Genetic association and functional analysis of rs7903456 in FAM35A gene and hyperuricemia: a population based study

Abstract

Recent studies have identified SNP rs7903456 of FAM35A to be associated with gout. Because of the close connections between hyperuricemia and gout, we hypothesized that the effect of rs7903456 on gout might be mediated by hyperuricemia or its related quantitative trait, uric acid level. We investigated the association between 31 SNPs of FAM35A, including rs7903456, and hyperuricemia based on 2,773 hyperuricemia patients and controls. We fitted a simple model for each of these 31 SNPs to screen the candidate SNP for further analyses. Moreover, we selected potential confounders and fitted a multivariate model to investigate the adjusted effects of the targeted SNPs. Both disease status of hyperuricemia and blood uric acid level were considered as the main phenotype. We have identified rs7903456 to be associated with hyperuricemia and uric acid level. The significant signal was identified between rs7903456 and uric acid level after adjusted by several potential confounders. Our findings showed that the T allele of rs7903456 could increase the uric acid level by ~10 mmol/L on average after adjusting several biochemical and clinical variables. Our findings indicated that the previously identified effects of rs7903456 on gout might partly be mediated by its effect on uric acid levels.

Single-nucleotide polymorphisms link gout with health-related lifestyle factors in Korean cohorts

“…These findings demonstrate that the PTPN11 is associated with rheumatoid arthritis and that SHP-2 contributes to the development of rheumatoid arthritis [43]. FAM35A (family with sequence similarity 35 member A), located on chromosome 10, encodes proteins with 835 amino acids and is ubiquitous, including the kidneys and other organs such as thyroid, duodenum, and small intestine [45]. Recently, it was confirmed that rs7903456 of FAM35A was associated with hyperuricemia and gout in Japanese and Chinese populations [7].…”