Association Study Between Gene Polymorphism And Gout Susceptibility Of Han And Tibetan In Tibet Pkateau

Backgroud: Gout is a most common inflammatory arthritis in men(>40 years), is caused by the presence of monosodium urate crystals in joints and connective tissues. Hyperuricemia, tophi and joint inflammation are three clinical features of gout. Current evidence suggests that heredity contributes to gout progression. To determine potential genetic associations with the gout risk, this study aims to investigate whether variations in SLC2A9, WDR1, CLNK, PKD2 and ABCG2 are associated with gout in Han population and Tibetan population.Methods: A total of fourty-seven single nucleotide polymorphisms(SNPs) associated with gout risk were captured from previous genome-wide association studies. We performed a case-control study to evaluate the potential association of SNPs with gout in Han population and Tibetan population. All SNPs were genotyped in 438 cases(139 Han population, 299 Tibetan population) and 623 controls(309 Han population, 314 Tibetan population) using Sequenom Mass-ARRAY technology. ORs(adjusted for age and gender) and 95%CIs were estimated using unconditional logistic regression analysis, and SPSS 19.0 statistical packages, χ2 test, genetic model analysis and Haploview 4.2 were analyzed associations between SNPs and gout risk.Results: Using the chi-square test, in Han populations, WDR1rs717614, CLNKrs10034180, CLNKrs16869430 and ABCG2rs12505410 were significantly associated with an increased risk of gout. In Tibetan populations, CLNKrs2108878, PKD2rs2725212, rs2725210, rs2725207, rs2728132, rs2725205 and rs2725203 were significantly associated with an increased risk of gout, ABCG2rs12505410 reduced the risk of gout.Using genetic models analysis, In Han populations, SLC2A9rs6823877 showed a protective effect of gout in the additive model, the genotype “GG” of WDR1rs717614 was significantly associated with an increased risk of gout in the recessive model, the genotype “A/G-A/A” of CLNKrs10034180 was significantly associated with an increased risk of gout in the dominant model, the genotype “C/T-T/T” of CLNKrs16869430 was significantly associated with an increased risk of gout in the dominant model, the genotype “C/T-C/C” of CLNKrs2041216 was significantly associated with an increased risk of gout in the dominant model, the genotype “A/G-G/G” of CLNKrs997219 was significantly associated with an increased risk of gout in the dominant model, ABCG2rs12505410 was significantly associated with an increased risk of gout in the additive model, the genotype “C/T-T/T” of ABCG2rs2622626 was significantly associated with an increased risk of gout in the dominant model. In Tibetan populations, the genotype “T/C-C/C” of ABCG2rs2231164 was significantly associated with a decreased risk of gout in the dominant model.Using Haploview 4.2 analysis, in Han populations and Tibetan populations, we detected four blocks of chromosome 4p16.1, two blocks of SLC2A9 SNPs and two blocks of CLNK SNPs. We detected three blocks of chromosome 4q22.1, two blocks of PKD2 SNPs and one block of ABCG2 SNPs.In addition, using haplotype analysis, the CLNK haplotype “GTCAT” showed an increased gout risk in Han subjects. The PKD2 haplotypes “GGACA” and “AAAAG” were associated with increased gout risk in Tibetan subjects, but after adjusting for age and gender, these haplotypes were not associated with gout risk.Conclusions: Our results, combined with those from previous studies, suggest that genetic variation in SLC2A9, WDR1, CLNK, PKD2 and ABCG2 may influence gout susceptibility in the Han population and in the Tibetan population.