Background/Purpose:

ITGAM (Integrin-α-M, also known as CD11b) gene located at chromosome 16p11.2, encodes for the α-chain of Integrin-α_Mβ₂, a leucocyte specific integrin receptor, also known as complement receptor 3 (CR3). It is important in the adherence of leucocytes to stimulate endothelium and in the phagocytosis of complement coated particles such as apoptotic cells. Single nucleotide polymorphism (SNP) rs1143679 G/A in ITGAM gene encodes an amino-acid change from arginine to histidine at position 77 (R77H) which impairs the integrin-mediated cell adhesion of ligands and reduces phagocytosis of complement-coated particles, hence, predisposing to SLE. SNP rs1143679 has been shown to be associated with SLE in European, African, Hispanic or native American populations. We aimed to verify this association in North Indian population and to study the genetic relations between this SNP and sub-phenotypes of SLE.

Methods:

395 SLE patients (classified according to the 1997 ACR classification criteria for SLE) and 593 controls were enrolled. All samples were genotyped for SNP rs1143679 using TaqMan genotyping assay in Roche LC480 real-time polymerase chain reaction (PCR) system. A case-control association study and a genotype phenotype correlation were performed.

Results:

The mean age of the SLE patients was 30.7 years, and 94.3% were females. Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p > 0.05). Allele contrast showed that the variant allele A was associated with increased risk for SLE when compared with the G allele (OR = 1.63, 95% CI = 1.23 – 2.17, p < 0.001). A significant difference was detected both under recessive model [AA vs (GA + GG): OR = 4.31, 95% CI = 1.90 – 9.79, p < 0.01] and dominant model [(AA + GA) vs GG: OR = 1.18, 95% CI = 0.85 – 1.64] with regard to the distribution of genotype frequencies between SLE patients and healthy controls. On sub-phenotype analysis, an association was observed between SNP rs1143679 and oral ulcers, under the dominant model (OR = 1.65, 95% CI = 1.01 – 2.70, p < 0.05). None of the other clinical manifestations showed association with SNP rs1143679.

Conclusion:

SNP rs1143679 in ITGAM gene predisposes to SLE in North Indian population. In accordance with the results of the previous studies conducted in European, African, and Hispanic populations, ITGAM rs1143679 polymorphism is associated with SLE susceptibility in different ethnic groups.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-itgam-polymorphism-rs1143679-with-susceptibility-to-systemic-lupus-erythematosus-in-north-indian-population/