Polymorphisms in insulin-like growth factor 1 receptor and near PDZ domain containing 1 are associated with phenotypic gout in Chinese Han males

期刊連結：http://www.gouthyperuricemia.com

Objective: The rs6598541 insulin-like growth factor 1 receptor (IGF1R) gene, rs7224610 in hepatic leukemia factor (HLF) gene and rs1967017 near PDZ domain containing 1 (PDZK1) gene proved to be significantly associated with the risk of hyperuricemia and gout in patients of European and Polynesia descent. However, evidence for association with gout in the Chinese population is inadequate. Thus, we conducted this study to identify whether variants of these three loci affect gout susceptibility in Chinese Han males.
Methods: 932 gout patients and 1,124 healthy controls were recruited for this study. The final results were obtained by sequenator. Association with gout was tested by logistic regression with adjusted false discovery rate, and genotypephenotype analysis was also conducted.
Results: Rs6598541 and rs1967017 allele frequencies were significantly different between gout and control groups, but only rs1967017 showed a significant difference in genotype (rs6598541, P=0.033, OR=1.12 by allele level; P=0.099 by genotype level; rs1967017, P=0.009, OR=1.43 by allele level; P=0.015 by genotype level). rs7224610 was not replicated (rs7224610, P=0.990, OR=1.03 by allele level; P=0.802 by genotype level). With T-allele carriers of rs1967017 showing an increased risk of gout (OR=1.43, 95%CI=1.12-1.82), the recessive genotype TT had a higher risk possibility (P=0.024, OR=1.33, 95%CI=1.08-1.65).
Conclusion: We validated rs6598541 and rs1967017 to be associated with gout in Chinese Han male population and unrelated to urate levels. These alleles may cause gout by other means rather than affecting urate levels. This study provides the basis for possible new targets in diagnosis and treatment of gouty arthritis.