Study On The Relationship Between Paraoxonase-1 And Type 2 Diabetes Mellitus Complicated By Coronary Artery Disease

Background With the development of medical science, many new drugs and technology have been applied to clinical practice. The total mortality of coronary artery disease (CAD) has been decreasing, and the patients life quality has increased greatly. However, to those with type 2 diabetes mellitus (T2DM ) the profit from the advancement is little. Recent studies have found that there is a glycoprotein called paraoxonase-1 (PON-1) in serum, which is combined with HDL and can protect LDL from oxidation. Consequently serum PON-1 activity is negatively correlated with the development of atherosclerosis. Some investigators report that PON-1 Q/R polymorphism affects serum PON-1 activity, and it is one of the risk factors of T2DM complicated by CAD.Ob j ect i ve To reveal the relationship between PON-1 Q/R polymorphism, serum PON-1 activity and T2DM complicated by CAD in Chinese Han ethnic group and to provide objective evidence in the prophylaxes and management of T2DM complicated by CAD.Methods The subjects of the study consist of four groups: (1) T2DM group (22 men and 14 women, mean age 56 ? years); (2) CAD group (35 men and 6 women, mean age 60 ?13 years); (3) T2DM complicated by CAD group(14 men and 13 women, mean age 66 ? years); (4) normal-control group(21 men and 12 women, mean age 57 + 11 years). PON-1 Q/R polymorphism wasevaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and serum PON-1 activity was determined using paraoxon as substrate by measuring the increase rate in the absorbance at 405 nm due to formation of 4-nitrophenol.Resu I ts (1) The distribution of the PON-1 Q/R polymorphism in the four groups was QQ genotype: 22.2%(8/36) , 36.6%(15/41), 29.6%(8/27) and 39.4%(13/33); QR genotype: 41.7%(15/36), 41.5%(17/41), 33.3%(9/27) and 39.4%(13/33); RR genotype: 36.1%(13/36), 21.9%(9/41), 37.1%(10/27) and 21.2%(7/33), respectively. There is no significant difference among them ( x2 =4.95, P>0.05) . In the above four groups allele frequency was Q: 43.1%, 57.3%, 46.3% and 59.1%; R: 56.9%, 42.7%, 53.7% and 40.9% , respectively. There is no significant difference among them ( x -=5.27, P>0.05) .In the present population , the Q and R allele frequency is 0.52 and 0.48, respectively. (2) Serum PON-1 activity in T2DM, CAD, T2DM complicated by CAD and normal-control groups was 56.43?7. 92u/ml, 50.34+25.69 u/ml, 32.86?. 84u/ml and 74.85 ?7.72u/ml, respectively. Serum PON-1 activity in the former three groups was significantly low compared with the control group (p<0.05), and serum PON-1 activity in T2DM complicated by CAD group was also significantly lower than T2DM and CAD group. (3) There was no signicant difference in BMI, TC, TG, FBS and PON-1 activity among different genotypes. (4) Smoking, hypertension and T2DM made serum PON-1 activity decrease. (5) Single Logistic regression analysis revealed that age, hypertension, high FBS and low serum PON-1 activity increased the risk of T2DM complicated by CAD. (6) Multiple Logistic regression analysis revealed that hypertension and low serum PON-1 activity were the independent risk factors of T2DM complicated by CAD.Conclusions The present study suggests that (1) There is nosignificant correlation between PON-1 Q/R polymorphism and T2DM complicated by CAD. (2)Hypertension and low serum PON-1 activity are the independent risk factors of T2DM complicated by CAD. Therefore, the measures that can increase serum PON-1 activity are useful to prevent the great vessels complications of T2DM.