Interleukin10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR-RFLP technique was used to detect IL10 promoter genotypes at the positions of −1082 (G/A), −819 (C/T) and −592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of −1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21-5.82), p-value = 0.046]. The CC genotype in −819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26-9.07), p-value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15-3.01), p-value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of −592 SNP and decreased in AA genotype carriers of −1082. IL10 was also increased in SLE patients with CGT (−592/−1082/−819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of −592 and TT genotype carriers at the region of −819. SLEDAI was also elevated among patients with CGC (−592/−1082/−819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 -819(C/T), −1082(G/A) and −592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings. K E Y W O R D S haplotype, interleukin 10, polymorphism, promoter, systemic lupus erythematosus | 21 MOHAMMADI et Al.

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients

“…6 A recent study showed that the CGT haplotype in the order of −592, −1082 and −819 had a significantly higher frequency in the patient group than in controls in Iranian studies. 13 Also, they noted the frequency of CGC haplotype was higher in patients with a higher SLEDAI score. Schotte et al.…”

“…12 Several association studies have been conducted with IL-10 and SLE. 13,14 Based on the studies, it is observed that the promoter polymorphisms in the IL-10 gene are related to genetic susceptibility to SLE. 15 SNPs in both distal (3575 T/A, −2849 G/A, −2763 C/A) and proximal regions (−1082 A/G, −819 T/C, −592 C/A) have been reported to influence disease susceptibility among different populations.…”

Systemic Lupus Erythematosus Progression and role of Genetic Variation in IL-22 and FOXP3 gene in population of Lahore, Pakistan

“…Recently, a research is done in Iran. This research forecast the connotation of promoter polymorphism of gene Interleukin 10 along with the action of SLE [12]. There are certain susceptible genes which trigger the SLE.…”

Genetic and molecular biology of systemic lupus erythematosus among Iranian patients: an overview

“…There were IL-10 plasma up regulations in CC and AA genotype carriers of -592 and -1082, respectively. The CC and TT genotype carriers at − 592 and − 819 regions respectively had also increased SLEDAI score [47]. Disturbed immune tolerance and T/B lymphocytes activation results in production of autoantibodies.…”