HIPK2 polymorphisms rs2058265, rs6464214, and rs7456421 were associated with kidney stone disease in Chinese males not females.

BACKGROUND AND AIM

Recent studies have shown that genetic factors are involved in the development of kidney stone disease (KSD). A case-control association analysis was performed to investigate the association between homeodomain-interacting protein kinase 2 (HIPK2; OMIM *606868) polymorphisms and KSD.

METHODS

A total of 890 KSD patients and 920 healthy subjects were analyzed. Polymorphisms were genotyped using SNPscanTM high-throughput SNP classification technology. The genotypic and allelic frequencies in KSD patients and healthy individuals were analyzed using a Chi-square test.

RESULTS

The genotype and allele distributions of the three polymorphisms (rs2058265, rs6464214, and rs7456421 in HIPK2) displayed strong associations with KSD in males (rs2058265: odds ratio [OR] 2.480,95%confidence interval [CI] 1.205-5.106, p = 0.014; rs6464214: OR 2.466, 95%CI 1.198-5.078, p = 0.014; rs7456421: OR 2.846, 95%CI 1.362-5.947, p = 0.005; perallele: r2058265T, OR 1.357, 95%CI 1.073-1.715, p = 0.011; rs6464214G, OR 1.340, 95%CI 1.060-1.693, p = 0.014; rs7456421C, OR 1.356, 95%CI 1.073-1.713, p = 0.011). Patients carrying the T allele of rs2058265, the G allele of rs6464214, or the C allele of rs7456421 showed higher systolic blood pressure, creatinine, and uric acid levels compared with wild-genotype individuals after adjusting for age, gender, and body mass index (p < 0.005).

CONCLUSION

The association of HIPK2 gene polymorphisms with KSD was only observed in males but not in females. HIPK2 gene polymorphisms were also involved in the changes of KSD-related metabolic traits.