Myeloperoxidase G-463A and CYBA C242T genetic variants in gestational diabetes mellitus

Abstract

Oxidative stress plays an important role in the pathophysiology of gestational diabetes mellitus (GDM). We investigated the relationship between NADPH oxidase p22phox subunit (CYBA) C242T (rs4673) and myeloperoxidase (MPO) G-463A (rs2333227) genetic variants and GDM in 719 patients with GDM and 1205 control women. Clinical, metabolic, and oxidative stress parameters were analyzed. We found that frequencies of the A allele (15.6% vs. 12.3%) and GA + AA genotype (28.5% vs. 23.2%) of the MPO G-463A variation were significantly higher in patient with GDM than in the control women (OR = 1.318, 95% CI: 1.068–1.625, P = 0.010 for the dominant model; OR = 1.999, 95% CI: 1.040–3.843, P = 0.034 for the recessive model; OR = 1.320, 95% CI: 1.095–1.591, P = 0.004 for the allele model). Genotype GA + AA remained a significant predictor of GDM in a logistic regression model including age and BMI at delivery (OR = 1.282, 95% CI: 1.037 ‒ 1.583, P = 0.021). Furthermore, the -463A allele was associated with higher TG and the 242T allele was related to higher pre-pregnancy BMI and oxidative stress index in all subjects (P <0.05). The 242T allele was also associated with higher HOMA-IR but lower serum total antioxidant capacity in patients with GDM (P <0.05). We conclude that the MPO G-463A, but not the CYBA C242T, genetic variation, is associated with an increased risk of GDM in Chinese women. These two genetic polymorphisms may be linked to obesity, dyslipidemia, insulin resistance, and oxidative stress.

CYP2E1 C-1054T and 96-bp I/D genetic variations and risk of gestational diabetes mellitus in chinese women: a case-control study

“…Upregulation of placental inflammatory cytokines, oxidative stress-related genetic variants (myeloperoxidase G-463 A, CYBA C242T, CYP2E1 C-1054T, etc. ), glycation and oxidation of proteins caused by hyperglycemia were associated with unfavourable metabolic profiles, insulin resistance, increased oxidative stress, and state of chronic inflammation in patients with GDM, which might increase the risk of adverse perinatal outcomes [ 6 , 8 , 11 , 20 , 21 , 47 ]. In contrast with most of published data in literature [ 2 , 6 , 21 ], in the present study, we found that the gestational weight gain and the birth height and weight of neonates were lower, whereas the incidence of macrosomia were similar in the GDM group than in the control group.…”

“…It is associated with increased long-term health risks, including type 2 diabetes mellitus and cardiovascular diseases in mothers, and metabolic syndrome, overweight, and obesity in both the mother and offspring [ 3 , 7 – 10 ]. The etiology of GDM is unknown and may be related to genetic variants [ 11 – 13 ], increased oxidative stress [ 11 , 14 – 16 ], dyslipidemia [ 17 ], chronic inflammation [ 18 ], abnormal expression of placental hormones and cytokines [ 19 – 21 ], and assisted reproduction technology [ 22 ].…”

Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study

“…Oxidative stress is involved in the pathophysiological processes of pregnancy [ 8 , 10 – 13 , 20 ]. PON1 is one of the necessary antioxidant enzymes in circulation and crucial in regulating the metabolism of oxidized lipids and homocysteine (HCY) [ 12 , 14 – 16 ].…”