269 Single nucleotide polymorphisms (snps) of integrin-alpha-m (itgam) are associated with lupus nephritis (ln) in an asian systemic lupus erythematosus (sle) cohort

Abstract

Background

The Integrin-alpha-M (ITGAM) rs1143679 SNP has been associated with susceptibility to SLE and lupus nephritis (LN) in oriental Chinese and Thai populations. We previously found 13 ITGAM SNPs in linkage disequilibrium (LD) that were associated with susceptibility to SLE, but found no association with rs1143679.

Aim

To determine associations of ITGAM SNPs with SLE subphenotypes and autoantibodies.

Methods

We studied 248 patients fulfilling the 1997 ACR revised criteria for SLE. SLE-associated ITGAM SNP alleles were identified using custom-designed Immunochip arrays and gPLINK 1.062 software, with Bonferroni corrections for multiple comparisons. Associations of SLE-related ITGAM SNPs with SLE subphenotypes (malar or discoid rash, serositis, mouth ulcers, arthritis, haematological, renal or neurological involvement) and autoantibodies to dsDNA, Ro, RNP or Sm were determined with chi-square and Fisher's tests and logistic regression.

Results

All 13 SLE susceptibility ITGAM SNPs as well as the uncommon rs1143679 SNP (n=11) were associated with LN ( Table 1 ). The strongest association was with rs2359661 (p=0.002, uncorrected). Subjects with these SNPs were less likely to have discoid rash. There was a trend towards an association with anti-Sm. Logistic regression models for 11 SNPs retained the factors LN, discoid rash and anti-Sm, suggesting strong LD for these SNPs.

Conclusions

This study demonstrated novel ITGAM SNP associations with LN and confirmed the association of rs1143679 with LN. Most associated SNPs were in the regulatory region of ITGAM bearing promoter/enhancer histone marks and have been associated with expression levels in several cell types, suggesting modulation of levels of ITGAM expression to impact these subphenotypes.