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

Abstract

Background: Type 2 diabetes (T2D) is an inflammatory disease that may cause inflammatory responses if it is not controlled; and may also 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.

Association of Perilipin and Insulin Receptor Substrate-1 Genes Polymorphism with Lipid Profiles, Central Obesity, and Type 2 Diabetes in a Sample of an Iranian Population

“…Other studies showing inflammation in fat has an important role in the expansion of obesity-induced insulin resistance (40,41). In our previous studies, detected IL-6R polymorphism was related with obesity and risk diabetes (42). Therefore, we assumed that various genes were involved in the development of obesity, some lipid profiles, and diabetes.…”

Interleukin‐6 receptor rs2229238C/T and rs4845625T/C polymorphisms increase the risk of schizophrenia in an Iranian population: A pilot study

“…The specific primers were designed for each SNP based on the amplification‐refractory mutation system polymerase chain reaction method (Table ). Polymerase chain reactions for both SNPs, namely rs2229238 and rs4845625, were carried out using two sequence‐specific forward primers (F1 and F2) and a common reverse primer (R) through the creation of a 319 bp band and a 279 bp band, respectively …”

Association of nitric oxide synthase 3 gene polymorphism with the risk of type 2 diabetes

“…Although several environmental and lifestyle conditions are involved in diabetes, genetic factors are also important determinants (3)(4)(5)(6)(7)(8)(9). Several genes have been investigated, and nitric oxide (NO) synthase has attracted the interest of researchers because of its determinative role in production of NO in endothelial cells (10,11).…”

“…Samples from 500 unrelated individuals were collected from the Diabetes Center in Ali Asghar Hospital (Zahedan, Iran). All samples were collected following the guidelines of according to the American Diabetes Association (21) and previous works of the authors (7,22,23). A health questionnaire on the detailed status of the subjects' disease including age, gender, body mass index (BMI), fast blood sugar (FBS), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and total cholesterol (TC) was administered for all participants.…”