Polymorphisms in the SLC12A3 Gene Encoding Sodium-Chloride Cotransporter are Associated with Hypertension: A Family-Based Study in the Mongolian Population

Background/Aims: Hypertension or persistent high blood pressure (BP) is a leading cause of death worldwide. Extensive evidence indicates that the thiazide-sensitive Na⁺-Cl^- cotrans-porter (NCC) affects BP via regulation of renal sodium reabsorption. However, the relationship between genetic variants of the NCC-encoding SLC12A3 gene and hypertension in the Mongolian population is still ambiguous. In this study, we aimed to genotype an extended cohort of hypertensive Mongolian families for polymorphisms in the SLC12A3 locus. Methods: Eighty-eight families with a history of hypertension, including parents, offspring, and relatives underwent clinical testing. Family-based association tests and haplotype analysis were used to evaluate the association between hypertension and polymorphisms in the SLC12A3 locus. Results : We identified three single nucleotide polymorphisms (SNPs), one in the SLC12A3 coding region ( p = 0.05) and two in the intron ( p = 0.02 and p = 0.07), which were significantly associated with the hypertension phenotype. Haplotype-specific association tests confirmed the correlation of these SNPs with hypertension ( p < 0.05). Conclusion: These results suggest that SNPs in the SLC12A3 gene confer susceptibility to hypertension in the Mongolian population. Further research is needed to validate the functional role of SLC12A3 polymorphisms in hypertension.