INTRODUCTION. Insulin secretion impairment and decreased insulin sensitivity coexist in type 2 diabetes mellitus. Aim of the study was: 1) to search for the association of insulin resistance candidate gene markers, the TNF-α –308 G/A promoter polymorphism and the K121Q PC-1 variant, with type 2 diabetes in a Polish population; 2) to examine their influence on pre-diabetes quantitative traits.
MATERIALS AND METHODS. Overall 732 subjects were examined. For case-control analysis we included 612 individuals: 358 type 2 diabetes patients and 254 controls. To assess prediabetic quantitative traits we examined 120 normoglycaemic individuals (the mean age: 34.2 years, the mean BMI: 27.9) with a family history of type 2 diabetes. The insulin and glucose levels were measured during OGTT and secondary indices were calculated. The groups were genotyped using RFLP. For the case-control study χ² test was used. For quantitative traits a multivariate linear regression analysis was employed.
RESULTS. The allele distribution was similar in the group of patients and in the controls: (15.7%/84.2% vs. 14.0%/86.0%, p = 0.38, for the -308 G/A TNF-α polymorphism, and 12.9%/87.1% vs. 13.1%/86.9%, p = 0.86, for K121Q PC-1 variant, respectively). Similarly, there was no difference in the genotype distribution. However, the carriers of at least one TNF1-α A allele (28% of the analyzed subjects) showed a higher ratio of 120-min insulin to the fasting insulin versus GG carriers (5.9 ± 6.5 vs. 3.4 ± 2.4; p = 0.04). Moreover, some additional differences were found for both markers in stratified analyses based on BMI, gender and age at examination.
CONCLUSION. Both examined markers, the TNF-α –308 G→A promoter polymorphism and the K121Q PC-1 variant, seem to influence the prediabetic quantitative traits in a Polish population. However, in case-control study we did not find the evidence of their association with type 2 diabetes in a Polish population.