JankovicV1, Ncbi, Checkpoint, bibRecord, 000072

Fibroblast Growth Factor 20 Polymorphisms and Haplotypes Strongly Influence Risk of Parkinson Disease

Identifieur interne : 000072 ( Ncbi/Checkpoint ); précédent : 000071; suivant : 000073

Fibroblast Growth Factor 20 Polymorphisms and Haplotypes Strongly Influence Risk of Parkinson Disease

Auteurs : Joelle Van [États-Unis] ; Maher Noureddine [États-Unis] ; Raja Kittappa ; Michael Hauser [États-Unis] ; William Scott [États-Unis] ; Ron Mckay ; Fengyu Zhang [États-Unis] ; Jeffrey Stajich [États-Unis] ; Kenichiro Fujiwara [États-Unis] ; Burton Scott [États-Unis] ; Margaret Pericak [États-Unis] ; Jeffery Vance [États-Unis] ; Eden Martin [États-Unis]

Source :

American Journal of Human Genetics [ 0002-9297 ] ; 2004.

RBID : PMC:1182076

Abstract

The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor (FGF20) in the survival of dopaminergic cells. FGF20 is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether FGF20 influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the FGF20 gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP, rs1989754 (P=.0006), and two SNPs, rs1721100 (P=.02) and ss20399075 (P=.0008), located in the 3′ regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (P=.0003), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (P=.0009). Our results strongly support FGF20 as a risk factor for PD.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182076

PubMed: 15122513
PubMed Central: 1182076

Affiliations:

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PMC:1182076

Le document en format XML

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<author><name sortKey="Fujiwara, Kenichiro" sort="Fujiwara, Kenichiro" uniqKey="Fujiwara K" first="Kenichiro" last="Fujiwara">Kenichiro Fujiwara</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Fibroblast Growth Factor 20 Polymorphisms and Haplotypes Strongly Influence Risk of Parkinson Disease</title>
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<author><name sortKey="Noureddine, Maher A" sort="Noureddine, Maher A" uniqKey="Noureddine M" first="Maher" last="Noureddine">Maher Noureddine</name>
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<placeName><region type="state">Caroline du Nord</region>
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<wicri:noCountry code="subfield">Bethesda</wicri:noCountry>
</affiliation>
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<author><name sortKey="Mckay, Ron" sort="Mckay, Ron" uniqKey="Mckay R" first="Ron" last="Mckay">Ron Mckay</name>
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<wicri:noCountry code="subfield">Bethesda</wicri:noCountry>
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<author><name sortKey="Zhang, Fengyu" sort="Zhang, Fengyu" uniqKey="Zhang F" first="Fengyu" last="Zhang">Fengyu Zhang</name>
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<author><name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey" last="Stajich">Jeffrey Stajich</name>
<affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="N0x948a890.0x975afc8">Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea>
</affiliation>
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<author><name sortKey="Fujiwara, Kenichiro" sort="Fujiwara, Kenichiro" uniqKey="Fujiwara K" first="Kenichiro" last="Fujiwara">Kenichiro Fujiwara</name>
<affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="N0x948a890.0x975afc8">Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC</nlm:aff>
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<placeName><region type="state">Caroline du Nord</region>
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<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
<affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="N0x948a890.0x975afc8">Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea>
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<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
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<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="N0x948a890.0x975afc8">Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC</nlm:aff>
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<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
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<front><div type="abstract" xml:lang="en"><p>The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor (FGF20) in the survival of dopaminergic cells. FGF20 is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether FGF20 influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the FGF20 gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP, rs1989754 (<inline-formula><italic>P</italic>
=.0006</inline-formula>
), and two SNPs, rs1721100 (<inline-formula><italic>P</italic>
=.02</inline-formula>
) and ss20399075 (<inline-formula><italic>P</italic>
=.0008</inline-formula>
), located in the 3′ regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (<inline-formula><italic>P</italic>
=.0003</inline-formula>
), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (<inline-formula><italic>P</italic>
=.0009</inline-formula>
). Our results strongly support FGF20 as a risk factor for PD.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
</region>
</list>
<tree><noCountry><name sortKey="Kittappa, Raja" sort="Kittappa, Raja" uniqKey="Kittappa R" first="Raja" last="Kittappa">Raja Kittappa</name>
<name sortKey="Mckay, Ron" sort="Mckay, Ron" uniqKey="Mckay R" first="Ron" last="Mckay">Ron Mckay</name>
</noCountry>
<country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle" last="Van">Joelle Van</name>
</region>
<name sortKey="Fujiwara, Kenichiro" sort="Fujiwara, Kenichiro" uniqKey="Fujiwara K" first="Kenichiro" last="Fujiwara">Kenichiro Fujiwara</name>
<name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name>
<name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<name sortKey="Noureddine, Maher A" sort="Noureddine, Maher A" uniqKey="Noureddine M" first="Maher" last="Noureddine">Maher Noureddine</name>
<name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
<name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
<name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name>
<name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey" last="Stajich">Jeffrey Stajich</name>
<name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<name sortKey="Zhang, Fengyu" sort="Zhang, Fengyu" uniqKey="Zhang F" first="Fengyu" last="Zhang">Fengyu Zhang</name>
</country>
</tree>
</affiliations>
</record>

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Fibroblast Growth Factor 20 Polymorphisms and Haplotypes Strongly Influence Risk of Parkinson Disease

Fibroblast Growth Factor 20 Polymorphisms and Haplotypes Strongly Influence Risk of Parkinson Disease

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