Heterozygous disruption of CMA1 does not affect blood pressure

It has been suspected that the mast cell chymase gene (CMA1) is important for the generation of angiotensin II and therefore might be associated with the pathogenesis of hypertension.

We sequenced the promoter region, exons, and exon-intron junctions of CMA1 and found 13 single-nucleotide polymorphisms, two of which were loss-of-function mutations. The loss-of-function mutations resulted in: (1) a premature stop codon; and (2) atypical splicing which creates a frame-shift and a stop codon. To elucidate the role of CMA1 in blood pressure regulation, we conducted an association study using these polymorphisms, including the loss-of-function mutations. The study population consisted of 1859 subjects, selected consecutively from the Suita study, an epidemiological cohort representing the general population in Japan.

There was no difference in the genotype distribution of the polymorphisms we studied between hypertensive and normotensive subjects, among either men or women. Moreover, neither of the heterozygous loss-of function mutations had a significant effect on blood pressure values.

Our data suggest that CMA1 is unlikely to influence blood pressure levels in the Japanese population.