Complex segregation and linkage analysis of familial gout in Taiwanese aborigines.
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).


CONCLUSIONS
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.
Wang
Wen Hsin
WH
Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Shun Jen
SJ
Wang
Tsu Nai
TN
Cheng
Li Shu-Chuan
LS
Feng
Yu Ping
YP
Chen
Chung Jen
CJ
Huang
Chun Hsiung
CH
Ko
Ying Chin
YC
D000328:Adult; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D006073:Gout / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000208:ethnology / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D035781:Siblings; D013624:Taiwan / Q000453:epidemiology
D005819:Genetic Markers