Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

Vaškú, Julie Anna Bienertová; Vašků, Anna; Dostálová, Zuzana; Bienert, Petr

doi:10.1007/bf02829953

Cited by 24 publications

(20 citation statements)

References 35 publications

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“…In type 1 diabetes, levels of the short isoform are higher than normal, whereas levels of the long isoform are normal (1,14). Although there is little evidence for leptin receptor deficiency in humans, polymorphisms in the long receptor isoform are associated with GDM (40) and may contribute to the complications associated with pregnancy in Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

“…Pregnant women who are overweight or obese or develop GDM all have high leptin levels and experience complications with parturition, frequently requiring a cesarean section (32,41). Polymorphisms in the leptin promoter, which is responsible for the expression of leptin specifically in adipose tissue, are associated with GDM (40). Interestingly, mice heterozygous for a leptin receptor mutation that is expected to reduce expression of the long isoform develop GDM despite an elevation in leptin levels (19,42,43).…”

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confidence: 99%

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Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice

Harrod

Rada

Pierce

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Harrod JS, Rada CC, Pierce SL, England SK, Lamping KG. Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice. Am J Physiol Endocrinol Metab 301: E362-E369, 2011. First published May 10, 2011 doi:10.1152/ajpendo.00696.2010.-In late gestation, enhanced myometrial contractility is mediated in part through increased Rho/Rho kinase. Since leptin, which is elevated in pregnancy and obesity, can directly depress myometrial function, we hypothesized that in leptin receptor-deficient mice, myometrial contractility would be greater in late pregnancy due to increased Rho/Rho kinase activity. To test this, we correlated RhoA and Rho kinase expression to contractility in myometrium from nonpregnant (NP) and late-pregnant (P18) heterozygous leptin receptor-deficient mice (db/ϩ) vs. wild-type (WT) mice. In NP mice, KCl-induced contractions were similar between WT and db/ϩ myometrium. However, the Rho kinase-dependent component of the contractions was greater in db/ϩ mice, along with an increased expression of Rho kinase. KCl-induced contractions increased in strength in myometrium from P18 WT and db/ϩ compared with NP. Although the contribution of Rho kinase to contractions was unchanged in P18 WT mice, it was decreased in P18 db/ϩ mice. The decrease in Rho kinase-dependent contractions in P18 db/ϩ mice coincided with reduced RhoA and Rho kinase expression relative to NP db/ϩ. Addition of high-fat-induced abnormal glucose utilization prevented changes in Rho kinase function. We conclude that abnormal leptin signaling increases expression and function of Rho kinase to maintain contractile function in NP myometrium and that during pregnancy the contribution of RhoA and Rho kinase expression to myometrial function is reduced despite an increase in myometrial contractility. Thus, other signaling mechanisms appear to compensate when leptin signaling is reduced to maintain contractile function during pregnancy. pregnancy; obesity; gestational diabetes CURRENTLY IN THE US, one in five pregnant women is obese, which is associated with increased perinatal mortality and morbidity and a fivefold increase in the average cost of prenatal care and hospital stay (12,20,28). Maternal complications in both overweight and obese women include development of gestational diabetes (GDM), preeclampsia, increased miscarriages and preterm births, poor labor progression, and failed spontaneous term deliveries (15,28,44). Because of the failure to deliver spontaneously in obese mothers, the number of postterm labor inductions and cesarean deliveries is high. The increased number of cesarean sections cannot be explained by an increased infant birth weight (44). These pregnancy-associated complications observed in obese women suggest that maternal obesity has a significant impact on myometrium, which is due possibly to abnormal uterine smooth muscle function. This notion is supported by the finding that both the force and frequency of spontaneous contractions are markedly decreased in my...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice

Harrod

Rada

Pierce

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…The association of polymorphisms in the leptin gene with GDM is controversial. Vaskú et al (2006) showed an association of leptin polymorphism -2548G>A with preeclampsia in GDM, but Yang et al (2016) failed to associate this polymorphism with GDM in a Chinese population.…”

Section: Discussionmentioning

confidence: 93%

“…Several adipokines, including leptin, are involved in the development of this resistance (Takhshid and Zare, 2015). The hormone leptin was first identified in adipose tissue and is known to be expressed in the placenta and fetal tissues (Vaskú et al, 2006). Leptin is considered a fetal growth factor able to maintain energy and metabolic balance during pregnancy (Xu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes

et al. 2017

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ABSTRACT. Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes. Women with gestational diabetes are at moderate risk of developing diabetes type 1 and 2 after pregnancy, in addition to complications to the fetus. We investigated the association of the polymorphisms rs7799039 (LEP) and rs13266634 (SLC30A8) in a case-control study in Euro-Brazilians with gestational diabetes (GDM, N = 180). Realtime PCR with fluorescent probes (TaqMan system) was applied to genotyping. All polymorphisms were in Hardy-Weinberg equilibrium. The minor allele frequencies, for healthy and GDM, respectively, for the A-allele (LEP gene rs7799039) were 40.3% (95%CI = 35-45%) vs 36.6% (95%CI = 31-42%), P = 0.345; and for the T-allele (SLC30A8 gene rs13266634) were 27.8% (95%CI = 23-32%) vs 23.5% (95%CI = 18-29%), P = 0.227. Genotype comparisons for both polymorphisms showed no significant difference (P > 0.05). The polymorphisms rs7799039 and rs13266634 were not associated with GDM in the population studied (P > 0.05). The minor allele frequencies for both polymorphisms were similar to those of other Caucasian populations.

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“…Previous research has shown that genetic variability in maternal LEP and LEPR gene might be involved in pathological processes in pregnancy, including preeclampsia and gestational diabetes mellitus (12,13), while the role of the LEP and LEPR gene in the IRSA has not been investigated. Therefore, we hypothesized that maternal genetic variability of the LEP and LEPR genes was associated with IRSA.…”

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confidence: 99%

Genetic variation in leptin and leptin receptor genes is a risk factor for idiopathic recurrent spontaneous abortion

et al. 2016

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AimTo determine whether maternal leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with idiopathic recurrent spontaneous abortion (IRSA).MethodsThis case-control association study conducted from 2010 to 2012 at the Department of Gynecology and Obstetrics, University Hospital Center Osijek and Clinical Institute of Medical Genetics Ljubljana included 178 women with a history of three or more IRSAs before the 22nd week of gestation and 145 women with at least two live births and no history of pathologic pregnancies during reproductive period. Polymorphisms of maternal LEP (rs7799039, rs2122627, rs11761556, rs10244329) and LEPR (rs1137101, rs7516341, rs1186403, rs12062820) were assessed by allele specific real-time polymerase chain reaction. Genotype distribution, allele frequencies, and frequency of haplotypes at LEP and LEPR genetic loci were determined.ResultsWe observed more frequent genotype for rs7516341 (nominal P = 0.034, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.38-0.97) and rs1137101 (nominal P = 0.048, OR 1.66, 95% CI 1.00-2.80) in the LEPR gene in patients than in controls, but these results did not remain significant after correction for multiple testing according to Bonferroni (adjusted P value threshold was set at 0.05). We did not observe differential distribution of genotype frequencies in the LEP gene between cases and controls. In patients with IRSA, GTCC haplotype in the LEPR gene locus was significantly less frequent than in controls (P = 0.00865, OR 0.45), contrary to ACTC haplotype (P = 0.0087, OR 1.98).ConclusionsWe showed that genetic variability in the LEPR gene was associated with IRSA, warranting confirmation on a greater number of patients and pathogenesis investigation.

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Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

Cited by 24 publications

References 35 publications

Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice

Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice

Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes

Genetic variation in leptin and leptin receptor genes is a risk factor for idiopathic recurrent spontaneous abortion

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