title: The Q192R polymorphism of the paraoxonase-1 (PON1) gene is associated with susceptibility to gestational diabetes mellitus in the Greek population.
abstract: A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in conferring susceptibility to both states. In the present study, we investigated the association between the PON1 gene and the risk for GDM in the Greek population and assessed for the first time its transcriptional efficiency. We studied 185 women with GDM and 104 non-diabetic controls for the PON1 polymorphism. For PON1 mRNA expression, peripheral leucocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the polymorphism, using real-time quantitative PCR. The RR genotype and the R allele of the PON1 Q192R polymorphism were significantly associated with an increased risk for GDM (p = 0.012 and p < 0.0001, respectively). Furthermore, there was no statistical correlation between the individual metabolic parameters tested and the three genotypes. Finally, the expression levels of PON1 mRNA in GDM patients did not exhibit any statistical difference compared with normal controls (p = 0.138). These data independently document that the Q192R polymorphism is closely associated with GDM susceptibility, while the PON1 gene expression is not impaired in GDM.
authors.affiliation: a First Department of Obstetrics and Gynecology, University of Athens School of Medicine , Athens , Greece.|b Department of Basic Medical Sciences , Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens , Athens , Greece , and.
authors.forename: Kalliopi I
authors.initials: KI
authors.lastname: Pappa
authors.affiliation: b Department of Basic Medical Sciences , Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens , Athens , Greece , and.
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.affiliation: c Department of Internal Medicine , First Endocrine Section and Diabetes Centre, Alexandra Hospital , Athens , Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Anastasiou
authors.affiliation: a First Department of Obstetrics and Gynecology, University of Athens School of Medicine , Athens , Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Loutradis
authors.affiliation: b Department of Basic Medical Sciences , Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens , Athens , Greece , and.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Anagnou
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006115:Greece; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Gestational diabetes mellitus; PON1 gene; oxidative stress; protein oxidation; type 2 diabetes mellitus