Heterozygous disruption of CMA1 does not affect blood pressure

J Hypertens. 2004 Jan;22(1):103-9. doi: 10.1097/00004872-200401000-00019.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

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

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / genetics*
  • Chymases
  • Cohort Studies
  • Diastole / genetics
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Heterozygote*
  • Humans
  • Hypertension / drug therapy
  • Hypertension / genetics
  • Japan / epidemiology
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Point Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • Serine Endopeptidases / genetics*
  • Statistics as Topic
  • Systole / genetics
  • Transcription, Genetic / genetics
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Serine Endopeptidases
  • CMA1 protein, human
  • Chymases