Transcription Factor 7-Like 2 (<i>TCF7L2</i>) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans

Watanabe, Richard M.; Allayee, Hooman; Xiang, Anny H.; Trigo, Enrique; Hartiala, Jaana; Lawrence, Jean M.; Buchanan, Thomas A.

doi:10.2337/db06-1682

Cited by 115 publications

(101 citation statements)

References 22 publications

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“…The effect size for GDM reported by this group was similar to that reported in patients with T2D. 33 Watanabe et al 38 observed that the T allele of the rs12255372 variant was more frequent among 94 Mexican-American women with previous GDM compared with 58 control subjects. These results suggest that TCF7L2 may be involved in GDM.…”

Section: Transcription Factor 7-like 2 (Tcf7l2)supporting

confidence: 64%

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

Robitaille

Grant

2008

Genetics in Medicine

130

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Gestational diabetes is a major public health problem because of its prevalence, its associated complications during pregnancy, and its increased risk for type 2 diabetes later in life. Insulin resistance is one of many physiological changes occurring during pregnancy, and when insulin resistance is accompanied by pancreatic ␤-cell insufficiency, gestational diabetes may develop. Several lines of evidence suggest that gestational diabetes shares a common etiology with type 2 diabetes and support the hypothesis that gestational diabetes serves as a window to reveal a predisposition to type 2 diabetes. Pregnancy is an environmental stressor that may catalyze the progression to a diabetic state in genetically predisposed women; therefore, identification of these women during pregnancy could decrease the occurrence of type 2 diabetes through targeted prevention. This review presents an overview of the genetics of gestational diabetes, focusing on human association studies with candidate genes common to both type 2 diabetes and gestational diabetes. Genet Med 2008:10(4):240 -250. Key Words: gestational diabetes mellitus, type 2 diabetes, genetics, pregnancy, association studiesGestational diabetes mellitus (GDM) is a major public health problem because of its prevalence and its associated complications during pregnancy. It is estimated that 4% of pregnancies in the United States are complicated by GDM, although the prevalence of GDM varies considerably among racial and ethnic groups. 1 Uncontrolled GDM increases the risk of adverse neonatal outcomes such as macrosomia, birth injuries, neonatal hypoglycemia, neonatal cardiac dysfunction, and stillbirth. 2 In addition to increasing the risk of adverse infant outcomes, GDM also has high predictive value for later development of type 2 diabetes (T2D) in the mother and in her offspring. Women who experience GDM have increased risk of developing T2D after pregnancy, ranging from 17% to 63% within 5-16 years after pregnancy depending on the population and other risk factors. 3 Additionally, offspring of mothers with GDM are more likely to be obese and display impaired glucose tolerance during adolescence than are offspring of nondiabetic mothers. Thus, diabetes during pregnancy is not only associated with the later risk of diabetes in mothers but also with metabolic changes that may lead to the development of diabetes in their offspring. 4 This observed connection between GDM and risk of T2D strongly suggests that GDM can serve as a window revealing a predisposition to T2D, with pregnancy as the environmental stressor that catalyzes progression to a diabetic state in predisposed individuals. 5 Several lines of evidence support the above hypothesis. First, GDM shares several risk factors with T2D, including high body mass index (BMI), history of abnormal glucose tolerance, diabetes in a first-degree relative, and membership in an ethnic group with a high risk of T2D. 6 Second, GDM and T2D share similar pathophysiologies: women undergo major physiological changes during pregn...

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Section: Transcription Factor 7-like 2 (Tcf7l2)supporting

confidence: 64%

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

Robitaille

Grant

2008

Genetics in Medicine

130

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“…In addition, a similar association was found in a meta-analysis of four studies (Watanabe et al, 2007;Cho et al, 2009;Papadopoulou et al, 2011;Vcelak et al, 2012) regarding the T allele of rs12255372 and GDM risk; the pooled OR was 1.46 (95% CI 1.15 -1.84, P ¼ 0.002), without significant heterogeneity across studies (I 2 ¼ 48.3%; P for the Q statistic ¼ 0.122; Table IV, Fig. 2B).…”

Section: Genes and Genetic Variants Related To Insulin Secretionmentioning

confidence: 54%

“…Several previous reviews have mainly focused on the evidence regarding T2DM-associated common variants and GDM susceptibility (Watanabe et al, 2007;Robitaille and Grant, 2008;Konig and Shuldiner, 2012;Mao et al, 2012). Our systematic review provided a more comprehensive summary of the currently available evidence regarding GDM genetic variants.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants and the risk of gestational diabetes mellitus: a systematic review

Zhang

Bao

Rong

et al. 2013

Human Reproduction Update

236

208

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background: Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.methods: Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.results: Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (230G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P , 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P ¼ 0.002) per T allele of rs12255372.conclusions: In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.

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“…Several studies have examined candidate genes in women with and without GDM. Positive associations were shown for genes encoding glucokinase [11], calpain-10 [12], sulfonylurea receptor 1 [13], potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) [14], β 3 adrenergic receptor [15], plasminogen activator inhibitor 1 [16] and transcription factor 7-like 2 (TCF7L2) [17,18]. Except for the effects of TCF7L2 in Scandinavian women [17], no robust associations of genetic variants with GDM have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

et al. 2008

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Aims/hypothesis New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A−CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p=4.17×10 −9 ) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p=1.05×10 −7 ) in the CDKN2A−CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p=0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p=0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p=0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p=0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation Some of the type 2 diabetesassociated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.

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Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans

Cited by 115 publications

References 22 publications

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

Genetic variants and the risk of gestational diabetes mellitus: a systematic review

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

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