Background: Calcitonin-related peptide alpha (CALCA) is a neuropeptide that is a very potent vasodilator. It has been reported that CALCA knockout mice have a significantly elevated systolic blood pressure (BP). The aims of this study were to discover novel polymorphisms or mutations in the 5' flanking region of the human CALCA gene in Japanese subjects and to assess the association between this gene and essential hypertension (EH).
Methods: Japanese patients with EH (50.1 +/- 6.6 years old, n = 274) and age-matched Japanese subjects without EH (51.1 +/- 6.6 years old, n = 225) were recruited. The 5' flanking region of the human CALCA gene was searched to identify novel polymorphisms in the 20 EH patients using polymerase chain reaction (PCR) and a direct sequencing method. These novel polymorphisms, as well as the known single nucleotide polymorphisms (SNPs), were used for genotyping.
Results: We discovered a novel 2-bp microdeletion polymorphism in intron 1. The only three participants with 2-bp microdeletion polymorphism were found in the EH group. None of the subjects without EH had a 2-bp microdeletion polymorphism. The genotype and allele distribution of the 4 SNPs were not significantly different between the groups. All five polymorphisms were located in one haplotype block. The haplotype was constructed using, in order, rs1553005, 2-bp microdeletion polymorphism, and rs5241. There was a significant association between EH and the C-AGins-A haplotype (P = .00031).
Conclusions: A novel 2-bp microdeletion polymorphism was discovered in the CALCA gene. Based on the results of the haplotype-based case control study, the CALCA gene could be the susceptibility gene for EH.