Preliminary observations on ANGPT1 and ANGPT2 polymorphisms in systemic sclerosis: ANGPT2 rs2442598 and rs3739390 are associated with disease susceptibility and diffuse disease subtype

Pol Arch Intern Med. 2021 Dec 22;131(12):16121. doi: 10.20452/pamw.16121. Epub 2021 Oct 13.

Abstract

Introduction: Angiopoietin-1 (Ang-1) and -2 (Ang-2) concentrations were found to be associated with systemic sclerosis (SSc).

Objectives: We explored whether single nucleotide polymorphisms of Ang-1 (ANGPT1) and Ang-2 (ANGPT2) genes can predict SSc susceptibility in Polish Caucasian patients.

Patients and methods: Genotyping by reverse transcriptase–polymerase chain reaction and Sanger sequencing was performed in 48 patients with SSc and 38 controls.

Results: Individuals with the CC genotype of ANGPT2 rs2442598 were 3.29-fold more likely to develop SSc (odds ratio [OR], 3.288; 95% CI, 1.212–8.915; P = 0.02) compared with those carrying the CT variant. Subgroup analysis revealed that the G allele, CG, and CG+GG genotypes of ANGPT2 rs3739390 were associated with a 9-fold higher risk to develop a diffuse form of the disease compared with the C allele or CC genotype (OR, 9.00; 95% CI, 2.102–38.519; P = 0.002 and OR, 9.00; 95% CI, 1.112–72.824; P = 0.03, respectively) and patients carrying the CG variant presented with higher serum Ang-2 levels than those carrying the CC variant (P = 0.001). On the contrary, the likelihood of a diffuse disease subtype was 8.77-fold lower for the TT+AT than for the AA genotype of ANGPT1 rs2507800 (OR, 0.114; 95% CI, 0.014–0.932; P= 0.04). The C allele of ANGPT2 rs3739390 was associated with a 4.83-fold lower risk of digital ulcers (OR, 4.833; 95% CI, 1.089–21.437; P= 0.03).

Conclusions: We concluded for the first time in the literature that the ANGPT2 rs2442598 polymorphism might represent a susceptibility locus for SSc, whereas the ANGPT2 rs3739390 and ANGPT1 rs2507800 variants may affect the disease profile.

MeSH terms

  • Angiopoietin-1* / genetics
  • Angiopoietin-2* / genetics
  • Disease Susceptibility
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Scleroderma, Systemic* / genetics

Substances

  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiopoietin-1
  • Angiopoietin-2