Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3. Methods A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM). Results Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype= 2.82; 95%CI [1.45–5.46]/OR for G allele= 1.97; 95%CI [1.36–2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05). Conclusion This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.
Systemic lupus erythematosus (SLE) is an autoimmune disorder with multifactorial etiology characterized by a high level of antibodies directed against nuclear and other cellular antigens, multisystem inflammation, relapsing, and a variable course and prognosis. 1,2 Over 90% of cases of SLE occur in women, frequently starting during reproductive age (range 20-30 years). However, the peak of disease incidence among males is more than the age of 45 years. 3 Most common SLE manifestations include renal involvement, arthritis, serositis, hematological, neurological, skin lesions, and oral ulcers. 1,4 Several pieces of research show that genetic factors have an important part in the incidence of SLE. Twin studies report a concordance rate ranging 24%-35% for monozygotic twins and 2%-5% for dizygotic twins. 5 On the other hand, there is the familial aggregation of SLE, which means people with lupus often have family members with SLE or other autoimmune conditions (10%-20% compared to 1% of controls). 6,7 Recently, genome-wide association studies (GWAS) reported multiple single nucleotide polymorphisms and novel rare variants in several genes which have an immunological function in correlation with SLE risk. For example, 1 study reported rare variations in 98 SLE-associated
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