Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene
Identifieur interne : 001698 ( Istex/Corpus ); précédent : 001697; suivant : 001699Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene
Auteurs : N. Tu ; H. Chen ; U. Winnikes ; I. Reinert ; G. Marmann ; K. M. Pirke ; K.-U. LentesSource :
- Life Sciences [ 0024-3205 ] ; 1998.
Abstract
Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.
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DOI: 10.1016/S0024-3205(98)00555-4
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Tu</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Chen, H" sort="Chen, H" uniqKey="Chen H" first="H." last="Chen">H. Chen</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Winnikes, U" sort="Winnikes, U" uniqKey="Winnikes U" first="U." last="Winnikes">U. Winnikes</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Reinert, I" sort="Reinert, I" uniqKey="Reinert I" first="I." last="Reinert">I. Reinert</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Marmann, G" sort="Marmann, G" uniqKey="Marmann G" first="G." last="Marmann">G. Marmann</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Pirke, K M" sort="Pirke, K M" uniqKey="Pirke K" first="K. M." last="Pirke">K. M. Pirke</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lentes, K U" sort="Lentes, K U" uniqKey="Lentes K" first="K.-U." last="Lentes">K.-U. Lentes</name><affiliation><mods:affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Life Sciences</title><title level="j" type="abbrev">LFS</title><idno type="ISSN">0024-3205</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">64</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="PL41">PL41</biblScope><biblScope unit="page" to="PL50">PL50</biblScope></imprint><idno type="ISSN">0024-3205</idno></series><idno type="istex">9C745B2B3C731F2873C26C1DDF9A571AB5538FA4</idno><idno type="DOI">10.1016/S0024-3205(98)00555-4</idno><idno type="PII">S0024-3205(98)00555-4</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0024-3205</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>N. Tu</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>H. Chen</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>U. Winnikes</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>I. Reinert</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>G. Marmann</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>K.M. Pirke</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item><json:item><name>K.-U. Lentes</name><affiliations><json:string>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>human uncoupling protein-2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genomic organization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mutational analysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>obesity energy metabolism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>body weight regulation</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Short communication</json:string></originalGenre><abstract>Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.</abstract><qualityIndicators><score>7.193</score><pdfVersion>1.2</pdfVersion><pdfPageSize>468 x 720 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>2275</abstractCharCount><pdfWordCount>4193</pdfWordCount><pdfCharCount>27385</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>371</abstractWordCount></qualityIndicators><title>Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene</title><pii><json:string>S0024-3205(98)00555-4</json:string></pii><refBibs><json:item><host><volume>15</volume><pages><last>224</last><first>223</first></pages><author></author><title>Nature Genet.</title></host></json:item><json:item><host><volume>15</volume><pages><last>272</last><first>269</first></pages><author></author><title>Nature Genet.</title></host></json:item><json:item><host><volume>235</volume><pages><last>82</last><first>79</first></pages><author></author><title>Biochem. 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Chem.</title></host></json:item><json:item><host><author></author><title>Publication No. 279</title></host></json:item><json:item><host><volume>61</volume><pages><last>PL 16</last><first>PL 9</first></pages><author></author><title>Life Sciences</title></host></json:item><json:item><host><volume>53</volume><pages><last>846</last><first>839</first></pages><author></author><title>Am. J. Clin. Nutr.</title></host></json:item><json:item><host><volume>16</volume><pages><first>1215</first></pages><author></author><title>Nucleic Acids Research</title></host></json:item><json:item><host><volume>5</volume><pages><first>84S</first></pages><author></author><title>Obesity Research</title></host></json:item><json:item><host><volume>43</volume><pages><last>264</last><first>255</first></pages><author></author><title>J. Cell Biochem.</title></host></json:item><json:item><host><pages><last>4065</last><first>4061</first></pages><author></author><title>Proc. Natl. Acad. Sci. USA</title></host></json:item></refBibs><genre><json:string>brief-communication</json:string></genre><host><volume>64</volume><pii><json:string>S0024-3205(00)X0201-9</json:string></pii><pages><last>PL50</last><first>PL41</first></pages><issn><json:string>0024-3205</json:string></issn><issue>3</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><title>Life Sciences</title><publicationDate>1998</publicationDate></host><categories><wos><json:string>science</json:string><json:string>pharmacology & pharmacy</json:string><json:string>medicine, research & experimental</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>pharmacology & pharmacy</json:string></scienceMetrix></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0024-3205(98)00555-4</json:string></doi><id>9C745B2B3C731F2873C26C1DDF9A571AB5538FA4</id><score>1.4208472</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/9C745B2B3C731F2873C26C1DDF9A571AB5538FA4/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/9C745B2B3C731F2873C26C1DDF9A571AB5538FA4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/9C745B2B3C731F2873C26C1DDF9A571AB5538FA4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) 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Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">U.</forename><surname>Winnikes</surname></persName><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">I.</forename><surname>Reinert</surname></persName><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">G.</forename><surname>Marmann</surname></persName><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">K.M.</forename><surname>Pirke</surname></persName><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">K.-U.</forename><surname>Lentes</surname></persName><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation></author></analytic><monogr><title level="j">Life Sciences</title><title level="j" type="abbrev">LFS</title><idno type="pISSN">0024-3205</idno><idno type="PII">S0024-3205(00)X0201-9</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">64</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="PL41">PL41</biblScope><biblScope unit="page" to="PL50">PL50</biblScope></imprint></monogr><idno type="istex">9C745B2B3C731F2873C26C1DDF9A571AB5538FA4</idno><idno type="DOI">10.1016/S0024-3205(98)00555-4</idno><idno type="PII">S0024-3205(98)00555-4</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>human uncoupling protein-2</term></item><item><term>genomic organization</term></item><item><term>mutational analysis</term></item><item><term>polymorphism</term></item><item><term>obesity energy metabolism</term></item><item><term>body weight regulation</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1997-10-24">Modified</change><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/9C745B2B3C731F2873C26C1DDF9A571AB5538FA4/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="sco"><item-info><jid>LFS</jid><aid>98005554</aid><ce:pii>S0024-3205(98)00555-4</ce:pii><ce:doi>10.1016/S0024-3205(98)00555-4</ce:doi><ce:copyright type="unknown" year="1998"></ce:copyright></item-info><head><ce:dochead><ce:textfn>Pharmacology letter Accelerated communication</ce:textfn></ce:dochead><ce:title>Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene</ce:title><ce:author-group><ce:author><ce:given-name>N.</ce:given-name><ce:surname>Tu</ce:surname></ce:author><ce:author><ce:given-name>H.</ce:given-name><ce:surname>Chen</ce:surname></ce:author><ce:author><ce:given-name>U.</ce:given-name><ce:surname>Winnikes</ce:surname></ce:author><ce:author><ce:given-name>I.</ce:given-name><ce:surname>Reinert</ce:surname></ce:author><ce:author><ce:given-name>G.</ce:given-name><ce:surname>Marmann</ce:surname></ce:author><ce:author><ce:given-name>K.M.</ce:given-name><ce:surname>Pirke</ce:surname></ce:author><ce:author><ce:given-name>K.-U.</ce:given-name><ce:surname>Lentes</ce:surname></ce:author><ce:affiliation><ce:textfn>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</ce:textfn></ce:affiliation></ce:author-group><ce:date-received day="15" month="6" year="1997"></ce:date-received><ce:date-revised day="24" month="10" year="1997"></ce:date-revised><ce:date-accepted day="27" month="8" year="1998"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>human uncoupling protein-2</ce:text></ce:keyword><ce:keyword><ce:text>genomic organization</ce:text></ce:keyword><ce:keyword><ce:text>mutational analysis</ce:text></ce:keyword><ce:keyword><ce:text>polymorphism</ce:text></ce:keyword><ce:keyword><ce:text>obesity energy metabolism</ce:text></ce:keyword><ce:keyword><ce:text>body weight regulation</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene</title></titleInfo><name type="personal"><namePart type="given">N.</namePart><namePart type="family">Tu</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H.</namePart><namePart type="family">Chen</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">U.</namePart><namePart type="family">Winnikes</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">I.</namePart><namePart type="family">Reinert</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Marmann</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K.M.</namePart><namePart type="family">Pirke</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K.-U.</namePart><namePart type="family">Lentes</namePart><affiliation>Laboratory of Molecular Neurogenetics, Center for Psychobiological and Psychosomatic Research (FPP), University of Trier, D-54290 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief-communication" displayLabel="Short communication"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><dateModified encoding="w3cdtf">1997-10-24</dateModified><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75–150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The HuCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon/intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7–13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3′-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.</abstract><note type="content">Section title: Pharmacology letter Accelerated communication</note><subject><genre>Keywords</genre><topic>human uncoupling protein-2</topic><topic>genomic organization</topic><topic>mutational analysis</topic><topic>polymorphism</topic><topic>obesity energy metabolism</topic><topic>body weight regulation</topic></subject><relatedItem type="host"><titleInfo><title>Life Sciences</title></titleInfo><titleInfo type="abbreviated"><title>LFS</title></titleInfo><genre type="journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">19981211</dateIssued></originInfo><identifier type="ISSN">0024-3205</identifier><identifier type="PII">S0024-3205(00)X0201-9</identifier><part><date>19981211</date><detail type="volume"><number>64</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="issue pages"><start>PL27</start><end>PL56</end></extent><extent unit="issue pages"><start>161</start><end>219</end></extent><extent unit="pages"><start>PL41</start><end>PL50</end></extent></part></relatedItem><identifier type="istex">9C745B2B3C731F2873C26C1DDF9A571AB5538FA4</identifier><identifier type="DOI">10.1016/S0024-3205(98)00555-4</identifier><identifier type="PII">S0024-3205(98)00555-4</identifier><recordInfo><recordContentSource>ELSEVIER</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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