Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin sensitivity and disposition in pregnant Han Chinese women.

AIMS/INTRODUCTION: Variants in cell cycle regulation genes, CDKAL1 and CDKN2A/2B, have been suggested to be associated with type 2 diabetes, and also play a role in insulin procession in non-diabetic European individuals. Rs7754580 in CDKAL1 and rs7020996 in CDKN2A/2B were found to be associated with gestational diabetes in Chinese individuals. In order to understand the metabolism mechanism of greatly upregulated maternal insulin signaling during pregnancy and the pathogenesis of gestational diabetes, we investigated the impact of rs7754580 and rs7020996 on gestational insulin regulation and procession. MATERIALS AND METHODS: We recruited 1,146 unrelated, non-diabetic, pregnant Han Chinese women (age 28.5 ± 4.1 years, body mass index 21.4 ± 2.6 kg/m(2)), and gave them oral glucose tolerance tests. The indices of insulin sensitivity, insulin disposition, insulin release and proinsulin to insulin conversion were calculated. Rs7754580 in the CDKAL1 gene and rs7020996 in the CDKN2A/2B gene were genotyped. Under an additive model, we analyzed the associations between the variants and gestational insulin indices using logistic regression. RESULTS: By adjusting for maternal age, body mass index and the related interactions, CDKAL1 rs7754580 risk allele C was detected to be associated with increased insulin sensitivity (P = 0.011), decreased insulin disposition (P = 0.0002) and 2-h proinsulin conversion (P = 0.017). CDKN2A/2B rs7020996 risk allele T was found to be related to decreased insulin sensitivity (P = 0.002) and increased insulin disposition (P = 0.0001). CONCLUSIONS: The study showed that cell cycle regulating genes might have a distinctive effect on gestational insulin sensitivity, ß-cell function and proinsulin conversion in pregnant Han Chinese women.

The Impact of Genetic Variants for Different Physiological Characterization of Type 2 Diabetes Loci on Gestational Insulin Signaling in Nondiabetic Pregnant Chinese Women.

We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m(2)) and gave them oral glucose tolerance tests. Matsuda index of insulin sensitivity, homeostatic model assessment of insulin resistance, indices of insulin disposition, early-phase insulin release, fasting state, and 0 to 120 minute's proinsulin to insulin conversion were used to dissect insulin physiological characterization. Several variants related to ß-cell function were genotyped. The genetic impacts were analyzed using logistic regression under an additive model. By adjusting for maternal age, BMI, and the related interactions, the genetic variants in ABCC8, CDKAL1, CDKN2A, HNF1B, KCNJ11, and MTNR1B were detected to impact gestational insulin signaling through heterogeneous mechanisms; however, compared with that in nonpregnant metabolism, the genetic effects seem to be eminently and heavily influenced by maternal age and BMI, indicating possible particular mechanisms underlying gestational metabolism and diabetic pathogenesis.

[Therapeutic efficacy of endoscopic variceal ligation to treat gastric varices: a study of 63 consecutive cases].

OBJECTIVE: To investigate the therapeutic efficacy of endoscopic variceal ligation (EVL) for treating various types of gastric varices (GV) by reviewing patient cases in order to identify the influencing factors of EVL-related recurrence and rebleeding. METHODS: The medical records of 101 GV cases treated by EVL in our department between January 2008 and October 2012 were retrospectively reviewed. The cases were grouped according to GV type: type 1 (GOV1, n = 63), type 2 (GOV2, n = 18), GOV1 coexisting with GOV2 (n = 11), isolated GOV1 (IGV1, n = 9), and GOV2 (IGV2, n = 0). Data from follow-up examinations (range: 1.5 - 48.0 months, average: 14.9 +/- 9.1 months) were extracted for analysis and included early (less than 72 h after EVL) and late (72 h to 6 weeks after EVL) rebleeding and recurrence. In addition, data from computed tomography (CT) or CT angiography (CTA), performed in 32 of the patients, were extracted to determine the influence of supplying veins, gastrorenal or splenorenal shunts, and portal vein and/or splenic vein diameters on GV recurrence. Data analysis was carried out by ANOVA, Chi-square, Fisher's exact or rank-sum tests, as appropriate. Kaplan-Meier analysis was used to evaluate the time of first recurrent bleeding, and the log-rank test was used to compare between-group differences. RESULTS: GOV2 and IGV1 varices were more severe than the varices of GOV1 (GOV2 and GOV1: u = -2.960; IGV1 and GOV1: u = -2.871; both P less than 0.05). GOV1 had a significantly lower recurrence rate than all other GV types (x2 = 7.054, P less than 0.05). The CT and CTA data indicated that all GV were supplied by left gastric veins, while 83.3% of IGV1 had blood supplementation by left gastric veins and short gastric or posterior gastric veins, and 100% of IGV1 had gastrorenal or splenorenal shunts. Approximately one-half of the total GV cases (56.3%, 18/32) had gastrorenal or splenorenal shunts, and this parameter was correlated with portal vein diameter (t = -2.766, P less than 0.05). The presence of gastrorenal or splenorenal shunts was correlated with both recurrence and rebleeding (P less than 0.05). CONCLUSION: EVL can effectively control bleeding and prevent rebleeding for GV; although, the best therapeutic efficacy and lowest rate of recurrence was achieved in GOV1 cases. The presence of gastrorenal or splenorenal shunts increases the risk of GV recurrence.

Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women.

BACKGROUND: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. METHODS: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI), association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG) levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD) between these variants was estimated by measures of D' and r(2). RESULTS: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p=8.04 × 10(-10), 5.49 × 10(-6), 1.89 × 10(-5) and 0.02, respectively). The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR) of 1.64 (p=8.03 × 10(-11)), 1.43 (p=1.94 × 10(-6)), 1.38 (p=1.63 × 10(-5)) and 1.24 (p=0.007), respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p=0.04). Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. CONCLUSIONS: The MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy.