Association Of CALCA Genetic Polymorphism With Essential Hypertension

Objective: Essential hypertention (EH) is a multifactorial disease. Itsoccurrence and development are the results of interactions between a varietyof genetic factors and environmental conditions. Investigation on associationof genetic factors such as genetic polymorphisms in candidate genes with EHsusceptibility will be helpful to understand the molecular mechanism for thedisease. In this study, a case-control study was performed to pinpoint whethersingle nucleotide polymorphisms (SNPs) in the genes coding for calcitoingene related peptideαandβ(CALCA and CALCB) were associated with EHsusceptibility in a Hunan Han population.Method: SNPs at CALCA and CALCB gene locus was recorded and analyzxedbased on the data deposited in NCBI database. One haplotype tag SNP(htSNP), i.e T→C transition 692 base pairs upstream(-692)of the translationinitiation codon of the CALCA gene (T-692C), was selected for thecase-control study. 293 subjects with EH and 208 controls were enrolled in thestudy. The cases and controls were matched with age and sex. The CALCAT-692C was genotyped by using PCR-based restriction fragment lengthpolymorphism (PCR-RFLP) method. DatA were analysed with SPSS softwareto compare c alleles and TC+CC genotypes in EH and controls, andunconditional logistic regression was applied to calculate the odds ratios ofrisk genotypes. Results: 1. The genotype frequencies of TT,TC and CC for CALCA T-692Cpolymorphism were 71.7%, 26.9% and 1.4%, respectively, in EH cases, and85.1%,14.9% and 0%, respectively, in the controls. The genotypic distributionwas in agreement with Hardy-Weinberg equilibrium in both cases andcontrols .2. Statistically significant difference in CALCA T-692C genotypicdistribution was observed between cases and controls (χ~2= 13.734, P＜0.05). 3.The frequencies of the C allele was 15.01% in EH group, and 7.45% in controlgroup, prevalence of C alleles in EH subjects and controls were significantuncomparable (P＜0.001). 4.When adjusted for sex, age, LDL, BMI, smokinghabits and familial history of EH, the results of logistic regression analysisshowed that the carders of C allele (TC+CC genotypes) was associated withincrease EH risk (OR=2.092, 95%CI: 1.308～3.347). 5. When stratified by sex,significant difference in the genotype distribution of CALCA T-692C wasobserved in female cases and controls, while no significant differenece in thegenotype distribution of CALCA T-692C genotypes TC+CC/TT of in malecases and controls was observed (P＞0.05).Conclusion: 1. Our study showed CALCA genetic polymorphism is associatedwith EH susceptibility. 2. Carders of at least C allele at polymorhic siteCALCA T-692C showed increased risk for EH.