Genetic variants of DNMT3A and systemic lupus erythematosus susceptibility

Mod Rheumatol. 2015 Jan;25(1):96-9. doi: 10.3109/14397595.2014.902296. Epub 2014 Apr 9.

Abstract

Objectives: A significant increase in DNA methyltransferase 3A (DNMT3A) transcript levels has recently been demonstrated in peripheral blood mononuclear cells from systemic lupus erythematosus (SLE) patients as compared to healthy individuals.

Methods: Employing high resolution melting curve analysis (HRM) and PCR-restriction fragment length polymorphism analysis, we assessed the frequency of five single nucleotide polymorphisms (SNPs) of this gene: rs2289195, rs7590760, rs13401241, rs749131 and rs1550117, situated in different linkage disequilibrium blocks of the DNMT3A gene in two hundred and fifty seven women with SLE and six hundred and twenty five controls.

Results: The lowest p values of the trend test were observed for the DNMT3A -448A> G (rs1550117) SNP (ptrend = 0.0111). We also found that, in a dominant inheritance model, the DNMT3A -448A> G SNP may protect from SLE development [odds ratio (OR) = 0.494 (0.294-0.830), p = 0.0068, pcorr = 0.034]. Furthermore, we observed that the DNMT3A -448A > G SNP in dominant inheritance models may protect from immunologic manifestations of SLE [OR = 0.1753 (95% CI = 0.04976-0.6176, p = 0.0026, pcorr = 0.0468).

Conclusions: Our study demonstrates that the DNMT3A -448A> G SNP might protect from SLE and its immunologic manifestations in a sample from the Polish population.

Keywords: DNMT3A; Polymorphisms; SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methyltransferase 3A
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • DNMT3A protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A