IL-17A haplotype confers susceptibility to systemic lupus erythematosus but not to rheumatoid arthritis in Mexican patients

Int J Rheum Dis. 2019 Mar;22(3):473-479. doi: 10.1111/1756-185X.13426. Epub 2018 Nov 5.

Abstract

Aim: Recent studies highlight the importance of the interleukin (IL)-17A cytokine in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). There are also reports of associations between some single nucleotide polymorphisms (SNPs) in IL-17A and RA but not SLE. Notably, these findings have not been replicated in all studied populations. The aim of this study was to investigate whether the IL-17A -737 T/C (rs8193036), -444A/G (rs3819024), -197G/A (rs2275913), and -121G/A (rs8193037) SNPs conferred susceptibility to SLE (or lupus nephritis) or to RA in a Mexican population.

Methods: The study included 1367 Mexican subjects, 501 with RA, 367 with SLE, and 499 healthy controls. IL-17A was genotyped using a TaqMan 5' allelic discrimination assay.

Results: Our results showed that the IL-17A -737 T/C, -444A/G, -197G/A, and -121G/A SNPs had similar genotype and allele frequencies in patients with SLE (or lupus nephritis) or RA and in controls. However, an IL-17A haplotype (TAGA) showed an association with SLE susceptibility (odds ratio 2.43, P = 0.004) but not with RA susceptibility.

Conclusions: These results confirm that the IL-17A -737T/C, -444A/G, -197G/A, and -121G/A SNPs are not risk factors for RA, but the IL-17A TAGA haplotype is a risk factor for SLE. This is the first report to document an association between IL-17A and SLE susceptibility in adults.

Keywords: IL-17A; haplotype; rheumatoid arthritis; single nucleotide polymorphism; susceptibility; systemic lupus erythematosus.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • Interleukin-17 / genetics*
  • Interleukin-17 / immunology
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • IL17A protein, human
  • Interleukin-17