Genetic Factors Contributing to Systemic Lupus Erythematosus in Tunisian Patients

Abstract

Systematic lupus erythematosus (SLE) is a multi system autoimmune disease characterized by autoantibodies production, multi-organ damage and complex genetic inheritance. Multiple genetic and environemental factors contribute to the pathogenesis of this disease. Recent genome-wide studies, have added substantially to the number of genes associated with SLE. We performed a case control study using 138 SNPs in 93 Tunisian patients affected with lupus and 162 healthy controls. All SNPs were genotyped in a Sequenom platform. To confirm some associations, associated SNPs were analyzed using logistic regression which allows the test of association with a given SNP by adjusting for the effect of confounding variables. Association was especially reported with rs3733197 (P=0.0026, OR=2.04), rs17266594 (P=0.046, OR=1.56) in BANK1 gene, rs2070197 (P=0.0016, OR=2.31), rs2004640 (P=0.024, OR=1.54), rs10954213 (P=0.035, OR=1.53) in IRF5 gene and rs7574865 (P=0.017, OR=1.77) in STAT4 gene: previously confirmed SLE susceptibility genes. rs1800629 (P=0.00036, OR=2.26), rs4147359 (P=0.026, OR=1.55) and rs11575812 (P=0.037, OR=1.57) of TNF-α, IR2RA and IL2 genes respectively were also associated with SLE. Haplotypic analysis reported 2 susceptibility haplotypes: TGG (P=0.00421, OR=1.87) in BANK1 and TCA (P=0.00177, OR=2.34) in IRF5 genes. Our results show that numerous genes, some with known immune related function predispose to lupus.

Interferon regulatory factor 5 gene polymorphism in Egyptian children with systemic lupus erythematosus

“…This was consistent with reports from adult patients with SLE from different ethnic groups; 17,32–34 a report from Tunisia on SNPs in patients with SLE has shown its association with rs2004640 and rs10954213 ( P = 0.024 and P = 0.035, respectively). 21 From different studies, there is general model of inheritance in which individuals carrying one copy of the rs2004640 T allele are at increased risk for SLE, and individuals carrying two copies have an even higher relative risk. 17…”

“…Reports including pSLE patients and two of the studied SNPs (rs2004640 and rs10954213) are scarce, 14,21 while rs2280714 was not included in any studies with paediatric lupus patients to the best of our knowledge. The largest number of pSLE cases was published in 2007 by Reddy et al.…”

“…The allele frequency of rs2280714 in the present cohort of healthy Egyptians is similar to most of those reported in the HapMap and other studied ethnic groups, while for rs10954213 and rs2004640 it was different from most populations in the HapMap and published data from different ethnic populations, except for rs10954213 in Caucasian, 43 Indian, 44 Han Chinese 45 and ASW, LWK, MKK and YRI from HapMap data and for rs2004640 in all 10 studied populations. 16,18,21,43,46–49…”

“…19,20 Only rs2004640 and rs10954213 have been studied once before in Arab patients with SLE from Tunisia. 21 To date, few reports studied correlation between rs2004640 and lupus nephritis (LN) and other SLE clinical manifestations, 18,22 while rs2280714 and rs10954213 have not been studied before in relation to SLE clinical and laboratory parameters.…”

Association of the IRF5 rs2070197 polymorphism with systemic lupus erythematosus: a meta-analysis

“…Recent genetic studies have reported an allelic association between IRF5 and SLE and a best association for the rs2070197 polymorphism [21][22][23][24][25][26][27].…”