| Objective: Based on the role of TAFI(thrombin activated fibrinolysis inhibitor) in balancing between the fibrinolysis and coagulation and no studies thus far have investigated the contribution of the TAFI genetic polymorphisms to type 2 diabetes mellitus(T2DM), we investigated the possible association of the TAFI activity-related two polymorphisms(505A/G,1040C/T) with increased risk of T2DM. At the same time we also carried out as a pilot study to examine the antigen and activity of TAFI in both patients and control groups.Methods: We studied the two allele frequencies of the 505A/G and 1040C/T polymorphisms which result in two amino acid substitutions: Ala for Thr at position 147 and Ile for Thr at position 325 in 157 type 2 T2DM patients and 140 healthy controls matched by age, gender, ethnicity and body mass index (BMI), using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) typing analysis. In addition, the TAFI-Ag and TAFI-Act were determined by enzyme link immunosorbent assay (ELISA) and chromogenic assay, respectively.Results: No significant differences of TAFI levels appeared between patients and controls at 505A/G. At 1040C/T ,the detected frequency for the T allele in the patients' group was significantly smaller in comparison to that of the control group (15.6% versus25.4%, respectively: P <0.05). This difference was due to the relative decrease of T/T homozygotes in the group of patients, in comparison to controls (P < 0.05, OR 0.33, 95%CI 0.12-0.91).The same pattern of significance was also observed between controls and the subgroups of patients with initial stages of T2DM categorized by the urine albumin excretion (UAEμg/ml)-to-creatinine (mg/ml) ratios (ACRs) while no significant difference was observed between controls and patients with latter stage of T2DM.Plasma TAFI:Ag and TAFI:Act were (119.82±35.53)% and (46.31±8.47)μg/ml in initial T2DM group, (130.52±46.39)% and (55.92±12.58)μg/ml in latter T2DM group, both being significantly higher than those of control group[TAFI:Ag(85.2±25.24)% and TAFI:Act(26.92±10.78)μg/ml].Conclusion: This study clearly indicates that at 1040C/T the frequency for the T allele is strongly associated with increased risk for T2DM in a subset of the general population. These results are in accordance to previous studies of constitutive expression and secretion of TAFI in T2DM, implying that the T allele confers protection against the onset of T2DM only in homozygosity, It may function as a recessive trait. It may be due to either unidentified properties of the 1040C/T polymorphism or of a strong linkage disequilibrium undefined between this polymorphism and another genetic locus. |
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