TY - JOUR
T1 - Genomewide scan for gout in Taiwanese aborigines reveals linkage to chromosome 4q25
AU - Cheng, Li Shu Chuan
AU - Chiang, Shang Lun
AU - Tu, Hung Pin
AU - Chang, Shun Jen
AU - Wang, Tsu Nai
AU - Ko, Allen Min Jen
AU - Chakraborty, Ranajit
AU - Ko, Ying Chin
N1 - Funding Information:
We thank the Mammalian Genotyping Service of the Marshfield Medical Research Foundation, with support from theNational Heart, Lung, and Blood Institute of the NationalInstitutes of Health (contract HV48141), for providing the genotyping. Some of the results of this article were obtained by S.A.G.E. software, which is supported by National Center for Research Resources grant RR03655.
PY - 2004/9
Y1 - 2004/9
N2 - 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 P = .0006; LOD = 4.3, P = 4.4 × 10-6 by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P = 1.3 × 10-6). 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.
AB - 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 P = .0006; LOD = 4.3, P = 4.4 × 10-6 by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P = 1.3 × 10-6). 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.
UR - http://www.scopus.com/inward/record.url?scp=4344684962&partnerID=8YFLogxK
U2 - 10.1086/423429
DO - 10.1086/423429
M3 - Article
C2 - 15252757
AN - SCOPUS:4344684962
VL - 75
SP - 498
EP - 503
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -