Abdolkarim Mahrooz1, Mohammad Bagher Hashemi-Soteh2, Masoud Heydari3, Ruzbeh Boorank3, Fatemeh Ramazani3, Ali Mahmoudi3, Anvarsadat Kianmehr4, Ahad Alizadeh5. 1. 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. Electronic address: amahrooz@mazums.ac.ir. 2. 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. 3. Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 4. Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran. 5. Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: a-alizadeh@razi.tums.ac.ir.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Mircea Vasile Milaciu; Ștefan Cristian Vesa; Ioana Corina Bocșan; Lorena Ciumărnean; Dorel Sâmpelean; Vasile Negrean; Raluca Maria Pop; Daniela Maria Matei; Sergiu Pașca; Andreea Liana Răchișan; Anca Dana Buzoianu; Monica Acalovschi Journal: J Clin Med Date: 2019-12-13 Impact factor: 4.241