The most effective polymorphisms of paraoxonase-1 gene on enzyme activity and concentration of paraoxonase-1 protein in type 2 diabetes mellitus patients and non-diabetic individuals: A systematic review and meta-analysis

• Published in: Diabetes research and clinical practice Vol. 152; pp. 135 - 145
• Main Authors: Hashemi, Mohammad Mostakhdem, Mousavi, Elham, Arab-Bafrani, Zahra, Nezhadebrahimi, Abbas, Marjani, Abdoljalal
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.06.2019
• Subjects: Enzyme activity; Enzyme concentration; Paraoxonase-1; Polymorphism; Type 2 diabetes mellitus; Enzyme activity; Type 2 diabetes mellitus; Paraoxonase-1; Enzyme concentration; Polymorphism
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2019.05.007

•The exact polymorphism which has the most effect on the activity of PON1 enzyme has not still been discovered in T2DM patients. In this study we could conclude that the RR genotype in case of Q192R polymorphism and also LL genotype in case of L55M polymorphism have the most affection on PON1 activity in T2DM patients, while PON1 concentration is less associated to these polymorphisms and their genotypes. Many studies have evaluated the association of paraoxonase-1 (PON1) gene polymorphisms with enzyme activity and concentration in type 2 diabetes mellitus (T2DM). However, the exact impact of these polymorphisms is not still obvious. Hence, we conducted a systematic review and meta-analysis to clarify the association of PON1 polymorphisms with its enzyme characteristics in T2DM patients and non-diabetic individuals. We searched electronic databases including PubMed, Web of Science, Embase and Scopus for publications by April 2018. The pooled response ratio (rr) for the association and their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effect model. Fifteen relevant studies fulfilled our inclusion criteria. The results showed a 1.25-fold increase in total PON1 activity in non-diabetic group against T2DM patients (p-value = 0.024). Also, only Q192R and L55M polymorphisms had sufficient studies to be included in the meta-analysis. All three genotypes of Q192R polymorphism showed significantly different activities between the study groups with the highest pooled effect size for RR genotype (rrQQ < rrQR < rrRR) while this difference was seen only in LL genotype of L55M polymorphism. Therefore, Q192R polymorphism was more correlated with type 2 diabetes mellitus. In case of concentration, there was no significant differences between two groups (p-value = 0.897). Current meta-analysis suggested that the observed difference of total PON1 activity was due to the different activity of various genotypes of PON1 enzyme in case of L55M and Q192R polymorphisms so that LL and RR genotypes had the most important role in the establishment of mentioned difference.