Evaluating the Effect of the rs2229238 and the rs4845625 Interleukin 6 Receptor Gene Polymorphisms on Body Mass Index and the Risk of Type 2 Diabetes in an Iranian Study Population

Background: type 2 diabetes (t2d) is an inflammatory disease that may cause inflammatory responses if it is not controlled; and mayalso lead to clinical manifestations such as retinopathy, nephropathy, and neuropathy. interleukin 6 (il6) is an important proinflammatory cytokine that controls the influence of systemic inflammation on acute phase responses. to work effectively, il6 must bind with its il6 receptor (il6r). objectives: the current study aimed to investigate the possible associations between two il6r polymorphisms, namely, rs2229238 and rs4845625, and their susceptibility to t2d. patients and methods: this case-control study was done on 250 t2d patients and 250 healthy individuals. the polymorphisms were genotyped using an amplification refractory mutation system-polymerase chain reaction (arms-pcr). results: our findings showed that either the rs2229238 or the rs4845625 variant was associated with t2d in a sample of the iranian population. the rs2229238 c/t polymorphism showed a strong significant difference in the ct genotype (or = 0.38, %95 ci = 0.23 - 0.65, p = 0.000), as well as in the tt genotype (or = 0.18, %95 ci = 0.05 - 0.63, p = 0.007) as a protective factor against t2d in both the patient and the control group. in contrast, the rs4845625 c/t polymorphism showed a significant difference in the ct genotype (or = 1.92, %95 ci = 1.15 - 3.23, p = 0.031) and in the tt genotype (or = 1.59, %95 ci = 1.08 - 2.38, p = 0.021) as a risk factor for t2d in both the patient and the control group. an investigation of the alleles relating to these single nucleotide polymorphisms (snps) showed that the t allele of rs2229238 (or = 0.34, %95 ci = 0.22 - 0.52, p = 0.000) and the t allele of rs4845625 (or = 1.43, % 95 ci = 1.11 - 1.84, p = 0.006) were significantly different between the subject and control groups, and that these two polymorphisms play a protective and a risk factor role in t2d, respectively. a statistical analysis of the demographic and clinical data showed no significant association between the cc genotype and the ct + tt genotype: in the patient group, with the exception of body mass index (bmi) (p = 0.023) in the rs4845625 polymorphism and in the control group, with the exception of hdl (p = 0.025) in the rs2229238 snp. conclusions: we identified a strong association between the t allele of il6r gene polymorphisms (rs2229238, rs4845625) and the risk of t2d in a protective role and as a risk factor, respectively. we also found different bmi and hdl values between the patient group and the control group, respectively in compare genotypes (ct+tt vs. cc). further studies on various ethnicities are necessary to verify our findings.