RECENT FINDINGS IN CLINICO-GENETICS ANALYSES FOR CLINICALLY-DEFINED GOUT
Hirotaka Matsuo 1), Masahiro Nakatochi 2), Akiyoshi Nakayama 1), Yusuke Kawamura 1), Yu Toyoda 1), Seiko Shimizu 1), Tappei Takada 3), Kimiyoshi Ichida 4), Nariyoshi Shinomiya 1), Yukinori Okada 5)
1) Department Of Integrative Physiology And Bio-Nano Medicine, National Defense Medical College 2) Division Of Department Of Nursing, Nagoya University Graduate School Of Medicine 3) Department Of Pharmacy, The University Of Tokyo Hospital 4) Department Of Pathophysiology, Tokyo University Of Pharmacy And Life Science 5) Department Of Statistical Genetics, Osaka University Graduate School Of Medicine
Gout has strong genetic factors. Here, we show our recent findings in the associations between gout and genetic factors as followings:
1) OAT10/URAT2 variant decreases gout risk
Background: OAT10/SLC22A13 has been identified as a urate transporter by in vitro analyses; however, its physiological impact on urate handling remains to be elucidated. We therefore investigated the association between genetic variation of OAT10 gene and gout susceptibility.
Methods: We examined all exons of OAT10 in 480 gout cases and 480 controls of Japanese male, followed by a replication study. Also, we characterized a newly identified OAT10 variant using cell-based functional analyses.
Results: We found that OAT10 c.1129C>T (R377C) has a significant protective effect on gout susceptibility(OR = 0.67; reciprocal OR = 1.49). Functional assay demonstrated that the R377C variant is functionally null as a urate transporter.
Conclusion: Considering the reported expression of OAT10 on the apical side of the renal proximal tubular cells, our results suggest that functional OAT10 could be physiologically involved in a supply route of urate into the blood as a novel renal urate reabsorber “URAT2”.
Reference: Higashino et al., Dysfunctional missense variant of OAT10/SLC22A13 decreases gout risk and serum uric acid levels. Ann Rheum Dis. 2020 79(1):164–6.