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The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy.

ABSTRACT: We carried out this meta-analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty-six case-control studies were included in the meta-analyses, in which 35 for the association between paraoxonase 1 activity and DM risk, 8 for diabetic macroangiopathy and 7 for diabetic microangiopathy. Paraoxonase 1 activity was significantly associated with the susceptibility of DM in pooled population (SMD = -1.37, 95% CI = -1.79 ? -0.96, P = .000), and Asians (SMD = -2.00, 95% CI = -2.56 ? -1.44, P = .000), but not in non-Asians (SMD = -0.44, 95% CI = -0.91 ? 0.03, P = .069). However, marked heterogeneity was existed (I2 = 98.10%, P = .000) and subgroup analyses failed to investigate the sources of heterogeneity. Then, meta-regression was performed and found that ethnicity could explain the observed between-study heterogeneity (P = .002). Meanwhile, significant associations were found between paraoxonase 1 activity and diabetic macroangiopathy (SMD = -1.06, 95% CI = -1.63 ? -0.48, P = .000) and diabetic microangiopathy (SMD = -0.72, 95% CI = -1.32 ? -0.13, P = .018). In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.

SUBMITTER: Wu D

PROVIDER: S-EPMC6111876 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy.

Wu Diling D Wu Chenfang C Zhong Yanjun Y

Journal of cellular and molecular medicine 20180707 9

We carried out this meta-analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty-six case-control studies were included in the meta-analyses, in which 35 for ...[more]

PMID: 29981194

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Project description:IntroductionPlenty of studies have focused on the associations of paraoxonase 1 Q192R and L55M genetic polymorphisms with diabetic macroangiopathy and microangiopathy susceptibility, but these associations remain controversial. Therefore, this meta-analysis was conducted to demonstrate these relationships.MethodsRelevant studies published in English or Chinese were identified in PubMed, Embase, Wanfang Database, and CNKI by applying specific inclusion and exclusion criteria. Statistical analyses were performed using the STATA 12.0 statistical software.Results25 Case-control studies were included in the meta-analyses: six on the association between paraoxonase 1 L55M genetic polymorphism and diabetic macroangiopathy risk, nine on the association between L55M and diabetic microangiopathy risk, 12 on the association between Q192R and diabetic macroangiopathy risk, and 12 on the association between Q192R and diabetic microangiopathy risk. Paraoxonase 1 L55M genetic polymorphism was significantly associated with diabetic microangiopathy susceptibility in the dominant model [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.33-0.83, P = 0.006], the homozygous model (OR 0.37, 95% CI 0.16-0.86, P = 0.021), the allelic contrast model (OR 0.62, 95% CI 0.43-0.90, P = 0.011), the recessive model (OR 12.04, 95% CI 8.02-18.06, P = 0.000), and the heterozygous model (OR 0.57, 95% CI 0.38-0.85, P = 0.006), but L55M was not significantly associated with macroangiopathy susceptibility. Paraoxonase 1 Q192R genetic polymorphism was significantly associated with diabetic macroangiopathy susceptibility in the homozygous model (OR 1.88, 95% CI 1.06-3.32, P = 0.030), the allelic contrast model (OR 1.31, 95% CI 1.02-1.69, P = 0.038), and the recessive model (OR 1.55, 95% CI 1.11-2.16, P = 0.010), but not in the dominant and heterozygous models. Meanwhile, there was no significant association between paraoxonase 1 Q192R genetic polymorphism and diabetic microangiopathy susceptibility.ConclusionParaoxonase 1 L55M and Q192R genetic polymorphisms play important roles in diabetic macroangiopathy and microangiopathy susceptibility. Further well-designed studies based on large samples are needed to confirm these results.

Project description:AimDNA methylation is thought to be involved in regulating the expression of key genes and inducing diabetic peripheral neuropathy (DPN). However, clinically, the level of whole-genome DNA methylation and its relationship with DPN remains unclear.Methods186 patients with type 2 diabetes mellitus (T2DM) admitted to the Second Affiliated Hospital of Soochow University since Jul. 2016 to Oct. 2017 were enrolled in the study, including 100 patients in the DPN group and 86 patients in the non-DPN group, diagnosed with Toronto Clinical Scoring System (TCSS). Clinical and biochemical characteristics between the two groups were compared, and the correlations with TCSS scores were analyzed. Furthermore, the levels of genomic DNA methylation of leukocytes, measured with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), were also analyzed between the two groups.ResultsAge, duration, triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), creatinine, uric acid (UA), blood urea nitrogen (BUN), and C-reactive protein (CRP) were significantly higher in the DPN group. Estimated glomerular filtration rate (eGFR) and the level of genomic DNA methylation were much lower in the DPN group. Spearman correlation analysis showed that TCSS was positively correlated with age, duration, UA, and CRP and was negatively correlated with body mass index (BMI), eGFR, and the level of genomic DNA methylation. Interestingly, multiple stepwise regression analysis showed that only duration, genomic DNA methylation, and eGFR had impacts on TCSS. The results also showed that the levels of genomic DNA methylation did not change significantly whether or not there was renal injury. Another multiple stepwise regression analysis showed that TCSS and BMI were the influencing factors of genomic DNA methylation. Finally, we found that genomic DNA methylation levels were decreased significantly in the DPN group compared with the non-DPN group when the duration is ≥5 years or BMI ≥ 25 kg/m2.ConclusionLow level of genomic DNA methylation is a relative specific risk factor of diabetic peripheral neuropathy in patients with type 2 diabetes.

Dataset Information

The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy.

Publications

The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy.

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