Relationship between the paraoxonase 1 gene glutamine 192 to arginine polymorphism and gestational diabetes mellitus in Saudi women

Al-Hakeem, Malak Mohammed; Abotalib, Zeinab; Alharbi, Khalid Khalaf; Khan, Imran Ali

doi:10.1016/j.clinbiochem.2014.07.005

Cited by 19 publications

(9 citation statements)

References 26 publications

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“…The R allele and the 192RR genotype are associated with increased predisposition to GDM in Saudi or Greek women [18,19]. However, in the present study, no significant differences were observed in the frequencies of the PON1 -108C/T and 192Q/R genotypes and alleles between Chinese women with and without GDM.…”

Section: Discussioncontrasting

confidence: 85%

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Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus

Zhou

Liu

et al. 2020

Journal of Diabetes Research

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Background. Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present study investigated the lactonase activities and status of PON1 and their association with PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Methods. This is a case-control study of 347 women with GDM and 288 women with uncomplicated pregnancies. PON1 levels and lactonase activities were analyzed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL), respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, and PON1 genetic polymorphisms were also analyzed. Results. PON1 lactonase activity and levels of TOS, TAC, and MDA were higher in the GDM women compared with the control women. The PON1 -108C→T genetic variation decreased the levels and lactonase activities of PON1 in a genotype-dependent manner in the patient and control groups. GDM patients with the PON1 -108TT genotype displayed lower NLA than those with the -108CC or -108CT genotype. GDM patients with the RR genotype of PON1 192Q/R polymorphism had significantly lower PON1 lactonase activities and NLA and tended to have decreased PON1 levels compared with those with the QQ or QR genotype. Multivariable regression analysis revealed that the PON1 -108C/T or 192Q/R variations, apolipoprotein (apo) A1, apoB, TAC, MDA, or age was significant predictors of the levels, lactonase activities, or NLA of PON1. Conclusions. The lactonase activities of PON1 are increased in women with GDM. PON1 genetic variants, increased oxidative stress, and abnormalities in lipoproteins may be associated with these changes.

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Section: Discussioncontrasting

confidence: 85%

“…The PON1 R isoform hydrolyzes lipid peroxides in vitro less efficiently than does the Q isoform [9]. The 192Q/R polymorphism has been reportedly associated with coronary heart disease [9,10], polycystic ovary syndrome [17], and GDM [18,19].…”

Section: Introductionmentioning

confidence: 99%

Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus

Zhou

Liu

et al. 2020

Journal of Diabetes Research

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“…However, PON1 inhibition by HDL and LDL may have applications in atherosclerosis prevention. 12 PON1 is a multifunctional enzyme involved in oxidant defense, and genetic variants in PON1 are associated with CVD. 13 PON1 is a major antioxidant with a protective role in CVD, and PON1 enzyme activity is decreased in patients with CVD.…”

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confidence: 99%

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Alharbi

Al-Nbaheen

Alharbi

et al. 2017

Annals of Saudi Medicine

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BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients.OBJECTIVETo investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients.DESIGNCase-control study.SETTINGTertiary care center, Riyadh.METHODSTwo hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis.MAIN OUTCOME MEASUREThe strength of association between the Q192R polymorphism and FH in the Saudi population.RESULTSWe confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05–3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13–3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09–2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population.CONCLUSIONIn conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH.LIMITATIONOnly a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

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“…The Q192R polymorphism was associated with CAD, gestational diabetes, obesity, and T2DM plus CAD; however, there was no association with stroke, Alzheimer’s disease, or breast cancer. 10 , 11 , 21 - 25 The mutation C698T in C5L2 has been found to have a positive association with T2DM in a Saudi population. 12 In the year 2011, 2 studies were carried out with the thrombophilic genes MTHFR, FVL, and PII in relation with T2DM in Russian and Iranian populations.…”

Section: Discussionmentioning

confidence: 96%

Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population

Alharbi

2015

SMJ

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Objectives:To investigate the role of amino acid substitution variants Q192R and C698T in the development of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a Saudi male population.Methods:This case-control study was carried out in 200 Saudi male individuals: 100 patients with G6PD deficiency, and 100 control subjects collected between July and August 2011 in the Taif region of Saudi Arabia. A total of 2100 male Saudi individuals were screened by a fluorescence spot test, and 100 with G6PD deficiency were selected. Two common variants PON1 (rs662) and C5L2 (rs149572881) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis.Results:The results showed that the R allele and QR genotype were associated with the Q192R polymorphism in PON1 (R versus Q odds ratio [OR], 1.72; 95% confidence interval [95% CI], 1.1-2.6; p=0.01; and QR versus QQ: OR, 1.98; 95% CI, 1.1-3.6; p=0.02). All the C698T genotypes and allele frequencies in C5L2 were almost similar in both the cases and controls (CT versus CC: OR, 2.04; 95% CI, 0.3-11.4; p=0.40; and T versus C: OR, 2.02; 95% CI, 0.3-11.1; p=0.41).Conclusions:These findings suggest the association of PON1 with G6PD deficiency in the Saudi male population studied herein. Future studies, including correlation analyses between the clinical features and genotypes in populations of different ethnicities, are warranted to confirm the disease association with these genetic mutations.

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Relationship between the paraoxonase 1 gene glutamine 192 to arginine polymorphism and gestational diabetes mellitus in Saudi women

Cited by 19 publications

References 26 publications

Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus

Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population

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