Genomewide scan for gout in taiwanese aborigines reveals linkage to chromosome 4q25.
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 NPL(all) statistic]; empirical 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.
Cheng
Li Shu-Chuan
LS
Division of Information Science, City of Hope Medical Center, Duarte, CA, USA.
Chiang
Shang-Lun
SL
Tu
Hung-Pin
HP
Chang
Shun-Jen
SJ
Wang
Tsu-Nai
TN
Ko
Allen Min-Jen
AM
Chakraborty
Ranajit
R
Ko
Ying-Chin
YC
D000328:Adult; D002894:Chromosomes, Human, Pair 4; D005192:Family Health; D018703:Founder Effect; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006073:Gout / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics; D008126:Lod Score; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D013624:Taiwan
D005819:Genetic Markers