Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Clin Chim Acta. 2018 Sep;484:40-46. doi: 10.1016/j.cca.2018.05.037. Epub 2018 May 19.
Genome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control.
We performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP. A mismatch-PCR/RFLP was applied for genotyping the PON2-A148G variant.
The variant PON1-Q192R in males (OR = 2.55, 95%CI 1.16-5.69, p = 0.023) and PON2-A148G in females (OR = 1.56, 95%CI 1.00-2.44, p = 0.059) were associated with T2D. Compared with the LL genotypes of PON1-L55M, HbA1c levels were significantly lower in the LM genotypes (p = 0.01) and MM genotypes (p = 0.032) in patients. Multiple linear regression analyses showed that among the study variants only the PON1-L55M variant as an independent variable significantly associated with glycemic control. This variant significantly influenced glycemic control in patients with poor glycemic control so that it was better with the following order: LL < LM < MM. Based on gamma correlation, there was a significant inverse association between the number of M alleles of the PON1-L55M and HbA1c levels (r = -0.261, p = 0.001).
Sex should be considered a confounding variable in association studies on the variants PON1-Q192R and PON2-A148G in T2D. Patients sharing the 55 M allele were prone to having good glycemic control. Our findings provide genetic evidence that the PON1-L55M variant may be a factor contributing to glycemic control.
基因组研究表明，编码对氧磷酶 1（PON1）和 PON2 的基因与葡萄糖代谢有关。本研究的目的是同时评估 PON1 和 PON2 基因的功能变异与 2 型糖尿病（T2D）易感性之间的关系，并确定它们是否会影响血糖控制。
我们进行了一项病例对照研究，共纳入 145 例新诊断的 T2D 患者和 148 名对照。通过基于 PCR 的 RFLP 对常见变异包括 PON1-Q192R、PON1-L55M 和 PON2-S311C 进行基因分型。应用错配 PCR/RFLP 对 PON2-A148G 变异进行基因分型。
男性 PON1-Q192R 变异（OR=2.55，95%CI 1.16-5.69，p=0.023）和女性 PON2-A148G 变异（OR=1.56，95%CI 1.00-2.44，p=0.059）与 T2D 相关。与 PON1-L55M 的 LL 基因型相比，PON1-L55M 的 LM 基因型（p=0.01）和 MM 基因型（p=0.032）患者的 HbA1c 水平明显降低。多元线性回归分析显示，在研究的变异中，只有 PON1-L55M 变异作为一个独立变量与血糖控制显著相关。该变异显著影响血糖控制不佳的患者，因此，其控制效果的顺序为：LL<LM<MM。基于伽马相关，PON1-L55M 的 M 等位基因数与 HbA1c 水平呈显著负相关（r=-0.261，p=0.001）。
在 T2D 中，PON1-Q192R 和 PON2-A148G 变异的关联研究中，应考虑性别为混杂因素。携带 55M 等位基因的患者更易获得良好的血糖控制。我们的研究结果提供了遗传证据，表明 PON1-L55M 变异可能是血糖控制的一个因素。
