Background: To assess the association of polymorphisms and haplotypes of the mineralocorticoid receptor (MR) (NR3C2) gene to the risk of essential hypertension (HTN) in a Spanish population.
Methods: This is a population-based study which included 1,502 subjects (748 women) >18 years old. Twenty-four polymorphisms of NR3C2 gene were analyzed by using SNPlex (Genotyping System based on OLA/PCR technology).
Results: Alleles of the single-nucleotide polymorphism (SNP) rs5522 were significantly associated with the risk of HTN, both in the recessive and codominant models adjusted by age, gender, and body mass index (BMI). Genotype GG of the rs5522 showed to be protective against HTN odds ratio (OR) 0.10 (0.02-0.56), P < 0.01. One haplotype, which included the G allele of the rs5522, was also associated with reduced risk of HTN and four haplotypes which included the A allele were associated with increased risk of HTN. When the 24-h urinary sodium excretion and the estimated glomerular filtration rate (eGFR) were added, they did not reduce the significance level. Interaction between genotypes of the rs5522 and quartiles of 24-h sodium excretion has been observed. In subjects with the AA genotype, those with higher urinary sodium excretion had the lowest risk to be hypertensive.
Conclusion: A functional polymorphism of the NR3C2 gene was associated with risk of HTN. The data provided in this study seems to give credit to the hypothesis of the participation of MR gene in the development of HTN, although further studies are necessary to better assess its real impact.