| Objectives:Diabetes is commonly believed to a disorder in which many systems or organs may be involved,such as vascular,kidney,skin,pituitary gland,immune system and the nerve system. Vascular disease of low extremity (VDLE) is one of the most common complications in the patients with T2DM. It has been confirmed that higher circulating interleukin-6 (IL-6) levels are found. Based on the previous study, IL-6 is a pro-inflammatory cytokine and major mediator of immune and the acute phase response, which is thought of playing an important role in the pathogenesis of T2DM. However,IL-6 protein may be affected by many pathologic and physiologic conditions. The measurement,only once, might be not predictive of disease in a given individual. Single nucleotide polymorphisms (SNP) within the IL-6 promoter region (-174G/C, -572C/G and -597G/A) may lead to the genetic change which in turn may affect circulating IL-6 levels and contribute to the risk of VDLE. These polymorphisms in IL-6 promoter may be a key factor contributing to the development of VDLE. So the objective of the present study was to investigate if the IL-6 gene promoter region polymorphisms (-174G/C, -572C/G and-597G/A) may be associated with VDLE. Materials and Methods:A total of 280 consecutive T2DM patients and 70 healthy subjects as control (164 males and 186 females, mean age 58.3±0.6 years) from the endocrine department of the Tianjin General Hospital were recruited in our study. According to their complications, the T2DM patients were subsequently divided into 4 groups: 1. Vascular group; 2. Vascular and neuropathic group; 3. Neuropathic group; 4. Non-complications group. Genomic DNA was extracted from leukocytes obtained from whole blood of each participant with the commercial DNA purification Kits. Three biallelic polymorphisms in the promoter of IL-6-174G/C,-572C/G and-597G/A were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serologic tests for IL-6, IL-6 receptor(IL-6R) were performed on 90 T2DM patients with the commercially ELISA kits,and so did the serologic tests for high sensitivity C-reactive protein(hsCRP ) on all subjects. Statistical Analysis was performed by using SPSS 11.5 for windows. Results:l.The genotypes of the promoter of IL-6 -174G/C,-572C/G and -597G/A were in Hardy-Weinberg equilibrium. In the total group patients and healthy subjects,except the haplotype and allele frequencies of IL-6 promoter of -174G/C-572C/G and -597G/A differed significantly between DM group and healthy control group. The haplotype and allele frequencies of IL-6 promoter of -572C/G had significantly difference between VDLE group (23.4%CC, 53.9%CG, 22.7%GG;allele frequencies:49.6%G, 50.4%C) and non- VDLE group (36.7%CC, 47.5%CG, 15.8%GG; allele frequencies: 60.4%G, 39.6%C). 2. By logistic regression analysis,we found that the polymorphism of IL-6 promoter -572C/G was an independent risk factor for VDLE in Tianjin Han population. 3. IL-6JL-6R and hsCRP in the serum showed elevated in T2DM patients than that in normal subjects. And so did in the patients with VDLE. The mean IL-6 and IL-6R in the serum were also elevated in the patients who had IL-6 promoter -572C/G with allele G(21.8± 1.0 pg/ml and 220.1+6.67 ng/ml,respectively) than that with allele C (18.5 + 0.9 pg/ml and 190.0 + 6.0 ng/ml.respectively). The mean IL-6 in the serum were higher in patients who had IL-6 promoter -597G/A with allele A(22.5 + 2.2pg/ml) than that with allele G (16.8 + 0.7pg/ml). Conclusion:1 .We found the polymorphisms of the allele and haplotype frequencies of IL6 promoter of -174G/C, -572C/G and-597G/A among the healthy subjects of Han... |
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