Relationship between rs4349859 and rs116488202 polymorphisms close to MHC-I region and serum urate levels in patients with gout.

Background: Gout is the most common inflammatory rheumatic disease and elevated levels of serum urate (SU) are the main cause for its development. Major histocompatibility complex class 1 (MHC-1) plays an important role in the development of multiple inflammatory diseases; however, there is little evidence of its involvement in gout. The present study focused on evaluating the association of the rs4349859 and rs116488202 single nucleotide polymorphisms (SNPs) close to the MHC-1 region in patients with gout.

Methods And Results: One hundred and seventy-six individuals of Mexican origin were included, of which 81 were patients with primary gout and 95 were healthy controls. The rs4349859 and rs116488202 SNPs were genotyped using TaqMan probes by allelic discrimination by real-time PCR. Serum concentrations of biochemical parameters were measured with enzymatic methods. Descriptive statistics were applied and P-values < 0.05 were considered significant. It was observed that the rs4349859 and rs116488202 SNPs showed significant association with the risk of gout (OR = 146, 95%CI = 44.8-480.2, P < 0.01; OR = 2885, 95%CI = 265-31398, P < 0.01, respectively). Our results also showed significantly higher serum SU levels in gout patients with respect to controls (P < 0.01) in the carriers of the GA genotype compared with the GG genotype of the rs4349859 variant, and in the carriers of the CT genotype compared with the CC genotype of the rs116488202 variant.

Conclusion: The study revealed that rs4349859 and rs116488202 SNPs close to MHC-I region confers strong susceptibility to gout in Mexican population, and the heterozygous genotypes of both were associated with higher levels of SU.