Complex segregation and linkage analysis of familial gout in Taiwanese aborigines

Abstract

Objective. 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.Methods. 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.Results. 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).Conclusion. 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.Among Taiwanese aborigines, especially Atayal, Bunun, and Paiwan adults, the prevalence of gout is particularly high (i.e., 15.2% in men and 4.8% in women versus 0.34% and 0.28%, respectively, in nonaboriginal men and women) (1). In comparison with Maori individuals in New Zealand (among whom the prevalence of gout is 10.2% in men and 1.8% in women) (2) and Caucasians in the West (among whom the prevalence of gout is ϳ1% in both men and women) (3), Taiwanese have nearly the highest prevalence of gout in the world.Hyperuricemia is one of the risk factors for gout. The X-linked hypoxanthine guanine phosphoribosyltransferase (HPRT) gene participates in the metabolism of uric acid. The gene HPRT Tsou

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