Gomathi Panneerselvam, Iyer Anandi Chandramouli, Murugan Ponniah Senthil, Sasikumar Sundaresan, Raj Nancy Bright Arul Joseph, Ganesan Divya, Nallaperumal Sivagnanam, Murugan Maruthamuthu, Selvam Govindan Sadasivam
Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Swamy Diabetes and Prashanthi Infertility Research Center, Chennai, India.
Gene. 2018 Apr 15;650:55-59. doi: 10.1016/j.gene.2018.01.094. Epub 2018 Feb 2.
Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population.
Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA.
The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients.
PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population.
胰岛素抵抗在2型糖尿病和心血管疾病的发病机制中起关键作用。最近，据报道对氧磷酶-1（PON1）在体外具有通过促进葡萄糖转运蛋白4（GLUT-4）表达来降低胰岛素抵抗的能力。PON1中的单核苷酸多态性（SNP）与酶活性和浓度的变异性相关。基于此，我们旨在研究PON1（Q192R和L55M）多态性与成年南印度人群发生胰岛素抵抗风险的关联。
本研究纳入了287例2型糖尿病患者和293例健康对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对所有研究对象的PON1（Q192R和L55M）错义多态性进行基因分型。采用酶联免疫吸附测定法（ELISA）测量空腹血清胰岛素水平。
与健康对照相比，2型糖尿病患者中QR/RR和LM/MM基因型的分布显著更高。此外，R和M等位基因与2型糖尿病显著相关，优势比分别为1.68（P<0.005）和2.24（P<0.005）。发现SNP 192 Q>R基因型与较高的体重指数、胆固醇、甘油三酯、低密度脂蛋白、空腹血清胰岛素和稳态模型评估的胰岛素抵抗（HOMA-IR）显著相关。此外，在成年2型糖尿病患者中，PON1 L55M的突变等位基因或基因型与较高的体重指数、甘油三酯、极低密度脂蛋白、空腹血清胰岛素和HOMA-IR相关。
PON1（Q192R和L55M）多态性可能在胰岛素抵抗的发病机制和易感性中起关键作用，从而导致南印度人群发生2型糖尿病。
