Author/Authors :
Galavi، Hamid Reza نويسنده Student Scientific Research Center, Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran , , Saravani، Ramin نويسنده Department of Clinical Biochemistry, Cellular and Molecular Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran , , Alamdari، Ali Reza نويسنده Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran , , Ranjbar، Nasrin نويسنده Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran , , Damani، Elhame نويسنده Department of Health Education and Promotion, School of Public Health, Zahedan University of Medical Sciences, Zahedan, IR Iran , , Nakhzari Khodakhier، Tooba نويسنده Department of Biology, Sistan and Balochestan Unviersity, Sistan and Balochestan, IR Iran ,
Abstract :
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). The current study aimed to investigate the possible associations between two IL6R polymorphisms, namely, rs2229238 and rs4845625, and their susceptibility to T2D. 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). 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. 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.
