KLHL3 single-nucleotide polymorphism is associated with essential hypertension in Chinese Han population

Abstract

Hypertension, including secondary and essential hypertension (EH) variants, is a multifactorial disease, affecting more than one billion people worldwide. Secondary hypertension results from mutations in the putative gene KLHL3 (Kelch-like protein 3); however, it has not been reported whether the KLHL3 gene polymorphisms are associated with EH. Here, we investigated the association between KLHL3 (rs2301708 and rs7444370) polymorphisms and EH in the Chinese Han population. This case-control study included 522 subjects-260 patients with EH and 262 normotensive controls matched for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and levels of Na+, K+, and Cl-. The distribution of functional rs2301708 and rs7444370 polymorphisms within the KLHL3 gene was assessed through polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP). There was no significant difference in allelic and genotypic frequencies of KLHL3 rs2301708 between the EH and normotensive groups; however, the rs7444370 T allele and CT genotype in females was significantly associated with a protective effect against EH (P=.001, P=.002; P=.019, P=.052), and the haplotype CT of rs2301708 and rs7444370 among females in the EH group was less than in the normotensive group (P=.000; P=.007). The KLHL3 rs7444370 variant could be a protective factor in the pathogenesis of females' EH.