Abstract
Objective
Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure in different European populations. The gene encodes the ad-iponectin receptor and the calcium-dependent cell-cell adhesion glycoprotein T-cadherin, with roles in neoangiogenesis and vascular remodeling. A meta-analysis of replication case-control studies showed significant evidence of association between the polymorphic variant rs11646213 in the CDH13 gene with arterial hypertension (AH). The aim of this study was to explore the possible association between the rs11646213 (CDH13) and the risk of AH in Bulgarians (Caucasian, Eastern European).
Materials and methods
We performed a case-control study to determine the prevalence of rs11646213 in the CDH13 gene in Bulgarian individuals; to evaluate whether this polymorphic variant was associated with the risk of AH in the Bulgarian population, and to determine the precise direction of influence. A total of 791 subjects were included in the current study. Of them, 297 were patients with AH and 494 – population-based controls from different parts of the country. Genomic DNA was extracted from venous blood samples. The polymorphism rs11646213 in the CDH13 gene was genotyped with the TaqMan SNP Genotyping Assay platform. Non-adjusted x2-based analysis was applied for the evaluation of CDH13 genotype and allele association with AH by using PLINK 1.07.
Results
The frequencies of CDH13 genotypes and alleles AA, AT, TT, A and T in the control group were 16,8%, 49,6%, 33,9%, 41,6% and 58,4% and 15,5%, 43,4%, 41,1%, 37,2% and 63,8% in the AH group, respectively. No significant genotype and allele associations were found in the general Bulgarian population. Interestingly, in subgroup analysis, the rs11646213 TA genotype showed a positive association with a decreased risk of AH (p = 0.01) in Bulgarian females.
Conclusions
In our study, we found a positive sex–dependent association between the rs11646213 TA genotype and decreased risk of AH in the female group. The contribution of CDH13 to the risk of developing AH remains unclear, especially in this sex-dependent manner and has to be clarified by further genetic and functional analyses.