The Association Of Paraoxonase2 Gene C311S Variation With CAD And IS In Chinese Type2 Diabetes Mellitus

Background: The paraoxonase gene family contains at least three members, including PONI, PON2 and PON3, which are located on chromosome 7q21.3~22J. Until recently, there has been little insight into the role of the respective gene products in human physiology and pathology. However, emerging evidence from biochemical and genetic experiments is providing clues about the role(s) of the products of these genes. For example, the PON1 gene product is serum paraoxonase, which is expressed mainly in the liver and which hydrolyzes organophosphates. Serum paraoxonase circulates on a subfraction of high- density lipoproteins and appears to use phospholipids on both low and high- density lipoprotein particles as a physiological substrate. This functional relationship could explain the reported associations between common variation in the PONI gene and phenotypes related to atherosclerosis and lipoprotein metabolism. In contrast, the PON2 mRNA is expressed ubiquitously, and to date there are no mechanistic experiments that yield insights into its physiological role. However, there have been reports of association between common variation in PON2 and some metabolic quantitative phenotypes, such as plasma lipoproteins, plasma glucose, birth weight and atherosclerosis. And the PON2 gene and the deduced protein are very similar with the PONI .Some reports show the genetic variation of PON2 affected PONlactivity. While the function of PON2 gene product is unknown, such genetic associations could point to the possible physiological role(s) of PON2. It may play a role in lipoprotein and glucose metabolism. At present, the role of the PON3 gene product is very poorly understood. Complementary lines of research should soon clarify whether there -4- might be merit in clinical testing for genetic variation in the paraoxonase gene family or whether the gene products might be good candidates for therapeutic interventions. Objective Our purpose is to investigate the association of the C3 uS polymorphism of PON2 gene with coronary artery disease and ischemic stroke in Chinese type2 diabetes mellitus patients. Methods 1. Subjects: The study groups include 117 control subjects, 119 CAD patients with or without DM, 110 ischemic stroke patients with or without DM, and 105 type2 diabetics without arteriosclerosis. 2. Methods: Genotype frequencies of C3 11 S polymorphism were studied by PCR-RFLP analysis with DdeI digestion. Results C3 uS polymorphism of PON2 gene was detected in Chinese with the C/S allele frequencies 0.145 and 0.855. The frequency distribution and allele frequencies of C3 uS were similar among the control, the CAD patients without DM, the ischemic stroke patients without DM, and the T2DM patients without CAD and IS, whereas the C3llallele frequency was higher (NO.05) in type2 diabetics with CAD or IS than in the other four groups. PON2-3 11 polymorphisms were correlated with glycaemic control, which was worse for the alleles in the order C>S in the type 2 diabetic patients. And we founded novel genetic associations between PON2-3 11 variation and variation in fasting plasma concentration of total cholesterol in the patients with arteriosclerosis (CAD or/and IS). Conclusion...