Genomewide scan for gout in Taiwanese aborigines reveals linkage to chromosome 4q25
Genomewide scan for gout in Taiwanese aborigines reveals linkage to chromosome 4q25
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DOI：
10.1086/423429
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发表时间：
2004-09-01
影响因子：
9.8
通讯作者：
Ko, YC
中科院分区：
文献类型：
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作者：
Cheng, LSC;Chiang, SL;Ko, YC
痛风是一种尿酸代谢紊乱。太平洋南岛人口，包括台湾原住民，高尿酸血症和痛风的患病率非常高，这表明整个太平洋地区都存在奠基者效应。我们在此报告台湾原住民部落21个多重家系与痛风的全基因组连锁研究。从家族聚类、早期痛风发病和临床严重表现的观察中，我们假设一个主要基因在该性状中起作用。利用分布在22个常染色体上的382个随机多态性标记，我们证明了4q25染色体上的D4S2623标记与痛风有高度显著的联系（非参数连锁[NPLall统计]P= 0.0002；经验；P= 0.0006； LOD=4.3，逻辑回归P=4.4 × 10(-6)）。当酒精消费作为协变量纳入模型时，LOD评分增加到5.66 （P=1.3x10(-6)）。包括血清尿酸和肌酐在内的数量性状也显示出与该区域的适度联系。据我们所知，这是第一个基因组扫描报告，以确定一个基因位点窝藏痛风易感基因。
Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPLall statistic]; empirical;, by P=.0006; LOD=4.3, P=4.4x10(-6) by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3x10(-6)). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene.