| Objective:Type 2 diabetes mellitus(T2DM) is a family of metabolic diseases induced by insulin secretion deficiency and/or insulin resistance, along with other risk factors such as obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, and coagulation abnormalities contribute to coronary artery disease(CAD). In addition, the complications caused by the T2 DM, such as diabetic nephropathy(DN), diabetic retinopathy(DR), macrovascular disease(MD) and cerebral infarction(CI) also seriously affect the quality of life of patients. Several potentially functional variants of paraoxonase 1(PON1) have been implicated in type 2 diabetes mellitus( T2DM), T2 DM pathogenesis complicated by the interaction of environmental factors and genetic factors in vivo. According to reports, paraoxonase 1(PON1) has many potential function mutations, some of which are considered Type 2 diabetes susceptibility. PON1 encodes a glycoprotein on the surface of high-density lipoprotein, and played a pivotal role in preventing the process of LDL oxidation. Studies have shown that paraoxonase 1 gene polymorphisms play an important role in the progression of type 2 diabetes. But individual studies have shown inconclusive results. In the present study, a meta-analysis was performed to examine the associations between two well-evaluated polymorphisms(rs662 and rs854560) in PON1 and T2 DM.Methods:1 The literature search and retrieval strategies. Search the literatures that had previously been published on PON1 gene polymorphism with T2 DM before July 2015 in Pubmed and China National Knowledge Infrastructure(CNKI) database. The key words of English were( "PON1" or "Paraoxonase 1") and( "type 2 diabetes mellitus" or "type 2 diabetes") and( "variant" or "polymorphism"). The key words of Chinese were "paraoxonase 1 " and " type 2diabetes." No language limitations were used. Additional studies were identified via a manual review of the reference lists of identified studies and review articles.2 The criteria of inclusion and exclusion. The following criteria were included: 1) using the case-control study design; 2) investigating the association between PON1 and Type 2 diabetes; 3) having sufficient genotyping data to assess the OR and 95%CI value range. Two authors independently assessed the eligibility. If there were disagreements, we resolved by discussion. Exclusion criteria: 1) case report; 2) data or the coarse risk assessment value cannot be obtained, even though contacted the author; 3) repeat studies; 4) abstracts and unpublished reports.3 Data extract. Data from each manuscript were extracted, which included the first author, year of publication, country of origin, ethnicity, complication type, source of control groups(population-based, hospital-based or mixed controls), genotype method, and the number of cases and controls. For studies including subjects of different ethnicities or countries, data were extracted separately. If the data was not available, study authors were contacted to request missing data.4 Statistical analysis. All analyzes were performed using STATA11.0 software. Following three genetic models were used: dominance model(AA+AB versus BB), recessive model(AA versus AB+BB), and homozygote model(AA versus BB). To assess the relationship of PON1 polymorphisms and Type 2 diabetes susceptibility by combined OR values and 95% CI. Value test and quantify heterogeneity with Q and I2 statistics measurement.Results:1 Literature search results: By the initial screening, we obtain a total of 186 literatures on the basis of the search strategy. 162 literatures failed to include. Eventually, 24 literatures were included. Among them, 23 articles on SNP rs662, 13 articles on the rs854560.2 According to the results of type 2 diabetes complications: literature on rs662 divided into four groups, namely: group A is all type 2 diabetes and healthy control group, there are 17 literatures involved; group B is type 2 diabetes without complications and healthy control group, the literatures involved are nine; group C is type 2 diabetes with complications and healthy control group, there are 12 literatures involved; D group is type 2 diabetes with complications and type 2 diabetes without complications group, there are 16 literatures involved. About rs854560, literatures divided into three groups, namely: group E is all Type 2 diabetes and healthy control group, the literatures involved are nine; group F is type 2 diabetes with complications and healthy control group, involving four literatures; group G is type 2 diabetes with complications and type 2 diabetes without complications group, literatures involved are five; as the number of literatures involved type 2 diabetes and healthy control group is less, it will not analyzed.3 The result of meta analysis on rs662 associated with Type 2 diabetes: group A in the general population, the pooled OR and 95% CI in dominance model, recessive model and homozygous model were 1.09(0.74, 1.61), 1.14(0.82, 1.58) and 1.23(0.79, 1.90),respectively, the result in Caucasian was similar. But in Asian the pooled OR and 95% CI in homozygous recessive model was 1.52(1.09, 2.11). Group B in the Asian population, the combined OR value and 95% CI in these genes model were 1.40(1.07, 1.84), 1.14(0.77, 1.70) and 1.52(1.10, 2.10), respectively. Group C in the Asian population, the combined OR value and 95% CI in these genes model were 1.37(0.99, 1.90), 1.39(1.04, 1.88) and 1.73(1.30, 2.29),respectively. Group D in the all population, the combined OR value and 95% CI of these three genes model were 1.27(0.96, 1.69), 1.21(1.03, 1.43) and 1.05(0.71, 1.56), respectively. In Asian population, the combined OR value and 95% confidence intervals in these genes model were1.35(0.98, 1.86), 1.23(1.04, 1.46) and 1.06(0.69, 1.64); In Caucasian, the combined OR value and 95% CI in these genes model were 0.96(0.41, 2.21), 1.00(0.56, 1.77) and 0.97(0.25, 3.82).4 The result of meta analysis on rs854560 associated with diabetes mellitus type 2: E group in the general population, the pooled OR and 95% CI in dominance model, recessive model and homozygous model were 0.78(0.60, 1.03), 1.00(0.63, 1.58) and 0.86(0.56, 1.33),respectively, the result in Caucasian was similar. But in Asian the pooled OR and 95% CI in dominance model were 0.71(0.58, 0.87); F group in the Asian population, the pooled OR and 95% CI of these genes model were 0.70(0.56, 0.89), 1.33(0.96, 1.83) and 0.98(0.67, 1.44),respectively; G group in all population, combined OR values and 95% CI of these three genes model were 0.84(0.66, 1.06), 0.81(0.54, 1.22) and 0.75(0.49, 1.16),respectively.Conclusions:The SNPs of PON1 gene rs662 was significantly associated with Type 2 diabetes,especially with T2 DM accompanied by complications, and R allele is a risk factor for T2 DM. While the rs854560 was significant associated with T2 DM that mainly exists in Asian population, and M allele is a protective factor. These results indicated that PON1 gene associated with Type 2 diabetes susceptibility. |
PDF Full Text Request