Angiotensin II Type 1 receptor (AGTR1) gene polymorphisms are associated with vascular manifestations in patients with systemic sclerosis (SSc)

J Renin Angiotensin Aldosterone Syst. 2016 Aug 3;17(3):1470320316659954. doi: 10.1177/1470320316659954. Print 2016 Jul.

Abstract

Introduction: Systemic sclerosis (SSc) shows variable clinical expression in different ethnic groups; vascular abnormalities are a prominent feature of this disease and its clinical expression may be influenced by genetic factors.

Patients and methods: Herein, we describe 15 polymorphisms of the renin-angiotensin-aldosterone pathway in 170 Mexican admixed SSc patients (defined as patients with Mexican ancestry for at least 3 generations) and 199 healthy controls. We determined the presence of angiotensin II Type 1 receptor (AGTR1), angiotensin converting enzyme (ACE) and Endothelin 1 single nucleotide polymorphisms (SNPs) using 5' exonuclease TaqMan genotyping assays on a 7900HT real-time fast polymerase chain reaction (PCR) system.

Results: These polymorphisms had a similar distribution between SSc patients and controls, but we found that the AGTR1 G-680T (rs275652) (p = 0.02; OR 3.5; 95%CI 1.2-10.4) and AGTR1 A-119G (rs275653) (p = 0.008; OR 4.2; 95% CI 1.5-12.1) polymorphisms were associated with severe vascular involvement in our SSc patients.

Conclusions: This is the first report of the association of these polymorphisms with vasculopathy in Mexican admixed SSc patients. Our findings suggested that the angiotensin II Type 1 receptor genotype may influence the clinical expression of vasculopathy in these patients. Functional analyses should follow.

Keywords: Angiotensin; Hispanic patients; angiotensin II Type 1 receptor; finger ulcers; fingertip ulcers; polymorphisms; renin-angiotensin-aldosterone system; scleroderma; vasculopathy.

MeSH terms

  • Adult
  • Blood Vessels / pathology*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Receptor, Angiotensin, Type 1 / genetics*
  • Scleroderma, Systemic / genetics*

Substances

  • Receptor, Angiotensin, Type 1