Wang Wen Hsin, Chang Shun Jen, Wang Tsu Nai, Cheng Li Shu-Chuan, Feng Yu Ping, Chen Chung Jen, Huang Chun Hsiung, Ko Ying Chin
Kaohsiung Medical University, Kaohsiung, Taiwan.
Arthritis Rheum. 2004 Jan;50(1):242-6. doi: 10.1002/art.11441.
The prevalence of gout and hyperuricemia in Taiwanese aborigines is remarkably high. Although previous studies have failed to find evidence of a major gene responsible for gout, the disease is thought to involve genetic predisposition. We sought to determine whether genetic factors for familial gout exist among Taiwanese aborigines, and, if so, their chromosomal location.
We first performed complex segregation analysis. The study sample comprised 945 relatives distributed in 64 pedigrees; among them, 261 affected members (including probands) were found. In all of the aboriginal probands with gout, the disease was diagnosed and confirmed by rheumatologists. Blood specimens were then collected from 127 individuals living in one community that was used in the segregation analysis (from 25 pedigrees, 36 nuclear families, and 112 full sibpairs), and sibpair linkage analysis and a combined transmission disequilibrium test (TDT) method were used to test the genetic components.
In segregation analysis, after adjusting for sex and age, an autosomal-arbitrary major gene model was found to fit the data best, with disease allelic frequency of 0.31 and susceptibility of 0.92. In sibpair analysis, there was a clustering of many flanking markers showing significant linkage, including D1S498 (regression coefficient -0.52), D1S2635 (regression coefficient -0.47), and D1S196 (regression coefficient -0.51), in the 1q21 region of chromosome 1 (all P < 0.005). Results of the combined TDT showed that the marker D1S484 was significantly associated (had linkage) with allele 1 and was transmitted more frequently than other markers to the affected offspring (P < 0.005).
Results of this study provide evidence of a genetic basis for familial gout in the aboriginal Taiwanese population and suggest that a susceptibility locus may be located in the 1q21 region of chromosome 1.
台湾原住民痛风和高尿酸血症的患病率显著较高。尽管先前的研究未能找到导致痛风的主要基因的证据，但该疾病被认为涉及遗传易感性。我们试图确定台湾原住民中是否存在家族性痛风的遗传因素，若存在，确定其染色体定位。
我们首先进行了复杂分离分析。研究样本包括分布在64个家系中的945名亲属；其中，发现261名受影响成员（包括先证者）。在所有患有痛风的原住民先证者中，该疾病由风湿病学家诊断并确认。然后从居住在一个社区的127个人中采集血样用于分离分析（来自25个家系、36个核心家庭和112对同胞对），并采用同胞对连锁分析和联合传递不平衡检验（TDT）方法来检测遗传成分。
在分离分析中，调整性别和年龄后，发现常染色体任意主基因模型最符合数据，疾病等位基因频率为0.31，易感性为0.92。在同胞对分析中，许多侧翼标记聚集显示出显著连锁，包括位于1号染色体1q21区域的D1S498（回归系数 -0.52）、D1S2635（回归系数 -0.47）和D1S196（回归系数 -0.51）（所有P < 0.005）。联合TDT的结果表明，标记D1S484与等位基因1显著相关（存在连锁），并且比其他标记更频繁地传递给受影响的后代（P < 0.005）。
本研究结果为台湾原住民家族性痛风的遗传基础提供了证据，并表明易感基因座可能位于1号染色体的1q21区域。
