The polymorphic variant rs11646213 in the CDH13 gene is associated with susceptibility to arterial hypertension in Bulgarian female subjects
DOI:
https://doi.org/10.2478/amb-2026-0040Keywords:
arterial hypertension, Bulgarian females, CDH13, polymorphismAbstract
Abstract. Objective: Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure in different European populations. The gene encodes the adiponectin 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 χ2-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.
References
Org E, Eyheramendy S, Juhanson P, et al. Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations. Hum Mol Genet. 2009;18(12):2288-96.
Popov VS, Brodsky IB, Balatskaya MN, et al. T-Cadherin Deficiency Is Associated with Increased Blood Pressure after Physical Activity. Int J Mol Sci. 2023;24(18).
Wain LV. Blood Pressure Genetics and Hypertension: Genome-Wide Analysis and Role of Ancestry. Curr Genet Med Rep. 2014;2:13-22.
Warren HR, Evangelou E, Cabrera CP, et al. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 2017;49(3):403-15.
Butler MG. Genetics of hypertension. Current status. J Med Liban. 2010;58(3):175-8.
Seidel E, Scholl UI. Genetic mechanisms of human hypertension and their implications for blood pressure physiology. Physiol Genomics. 2017;49(11):630-52.
Ehret GB, Caulfield MJ. Genes for blood pressure: an opportunity to understand hypertension. Eur Heart J. 2013;34(13):951-61.
Lee JH, Shin DJ, Park S, et al. Association between CDH13 variants and cardiometabolic and vascular phenotypes in a Korean population. Yonsei Med J. 2013;54(6):1305-12.
Yaacov O, Mathiyalagan P, Berk-Rauch HE, et al. Identification of the Molecular Components of Enhancer‑Mediated Gene Expression Variation in Multiple Tissues Regulating Blood Pressure. Hypertension. 2024;81(7):1500-10.
Lee D, Han SK, Yaacov O, et al. Tissue-specific and tissue-agnostic effects of genome sequence variation modulating blood pressure. Cell Rep. 2023;42(11):113351.
Zhao Y, Blencowe M, Shi X, et al. Integrative Genomics Analysis Unravels Tissue-Specific Pathways, Networks, and Key Regulators of Blood Pressure Regulation. Front Cardiovasc Med. 2019;6:21.
Lu X, Huang J, Wang L, et al. Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese. Hypertension. 2015;66(4):786-92.
Moreno C, Williams JM, Lu L, et al. Narrowing a region on rat chromosome 13 that protects against hypertension in Dahl SS‑13BN congenic strains. Am J Physiol Heart Circ Physiol. 2011;300(4):H1530-5.
adiponectin sensitivity in East Asian populations. Diabetes. 14. Gilibert S, Bataillard A, Nussberger J, et al. Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats. J Hypertens. 2009;27(6):1186-93.
Putku M, Kals M, Inno R, et al. CDH13 promoter SNPs with pleiotropic effect on cardiometabolic parameters represent methylation QTLs. Hum Genet. 2015;134(3):291-303.
Er LK, Wu S, Cheng T, et al. Genome-Wide Association Study on Adiponectin-Mediated Suppression of HDL-C Levels in Taiwanese Individuals Identifies Functional Haplotypes in CDH13. Genes (Basel). 2021;12(10).
Gao H, Kim YM, Chen P, et al. Genetic variation in CDH13 is associated with lower plasma adiponectin levels but greater 2013;62(12):4277-83.
Kitamoto A, Kitamoto T, Nakamura T, et al. CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass. J Atheroscler Thromb. 2016;23(3):309-19.
Vargas-Alarcon G, Martinez-Rodriguez N, Velazquez-Cruz R, et al. The T>A (rs11646213) gene polymorphism of cadherin‑13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population. Immunobiology. 2017;222(10):973-8.
Fava C, Danese E, Montagnana M, et al. A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome in Swedes. Am J Cardiol. 2011;108(10):1432-7.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 R. Tzveova, T. Yaneva-Sirakova, J. Matrozova, S. Vandeva, P. Atanasov, D. Pendicheva-Duhlenska, V. Mitev, R. Kaneva (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
You are free to share, copy and redistribute the material in any medium or format under these terms.
Journal Acta Medica Bulgarica 
