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Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with essential hypertension: sex-specific

Nicola Glorioso1, Victoria L M Herrera, Pia Bagamasbad

  • 1Hypertension and Cardiovascular Prevention Center, ASL n. 1-Universita di Sassari, Sassari, Sardinia, Italy.

Circulation Research
|April 21, 2007
PubMed

Insights

Essential hypertension susceptibility genes ATP1A1 and Dear were identified in a Sardinian cohort. These genes show stronger links in males and suggest distinct hypertension subtypes, aiding research into complex genetic causes.

Area of Science:

  • Human Genetics
  • Cardiovascular Disease Research
  • Hypertension Etiology

Background:

  • Essential hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases.
  • Identifying genetic susceptibility loci for hypertension is challenging due to its complex, multifactorial nature.
  • ATP1A1 and Dear are candidate genes linked to blood pressure regulation in rats, with human syntenic regions on different chromosomes.

Purpose of the Study:

  • To investigate the association of human ATP1A1 and Dear genes with essential hypertension.
  • To analyze the genetic contribution of these loci to hypertension susceptibility in a human cohort.
  • To explore sex-specific associations and potential haplotype-specific subsets of hypertension.

Main Methods:

  • Single-nucleotide polymorphism (SNP) haplotype analysis was performed on a case/control hypertension cohort from northern Sardinia.
  • Sex-specific haplotype analyses were conducted to identify gender-related differences in gene association.
  • Haplotype trend-regression analyses were used to assess the independence of ATP1A1 and Dear as susceptibility loci.

Main Results:

  • Significant associations were found between human ATP1A1 (P<0.000005) and Dear (P<0.03) with hypertension.
  • Stronger associations for both loci were observed in males compared to females.
  • Haplotype analyses revealed independent contributions of ATP1A1 and Dear and identified haplotype-specific associations with hypertension and normotension.

Conclusions:

  • ATP1A1 and Dear are identified as independent susceptibility loci for essential hypertension in the studied population.
  • Haplotype subtyping allows for the stratification of hypertension susceptibility and clinical heterogeneity.
  • Coexpression of ATP1A1 and Dear in renal and vascular cells suggests a potential pathogenic mechanism contributing to hypertension-related dysfunction.

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