A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

Abstract

Aims/hypothesis Genetic and epidemiological studies suggest an association between gestational diabetes mellitus and type 2 diabetes. Both are polygenic multifactorial disorders characterised by beta cell dysfunction and insulin resistance. Our aim was to investigate whether common genetic variants that have previously been associated with type 2 diabetes or related phenotypes would also confer risk for gestational diabetes mellitus. Materials and methods In 1,881 unrelated pregnant Scandinavian women (649 women with gestational diabetes mellitus, 1,232 non-diabetic control subjects) we genotyped the transcription factor 7-like 2 (TCF7L2 rs7903146), adiponectin (ADIPOQ +276G>T), peroxisome-proliferator activated receptor, gamma 2 (PPARG Pro12Ala), PPARGcoactivator, 1 alpha (PPARGC1A Gly482Ser), forkhead box C2 (FOXC2 −512C > T) and β3-adrenergic receptor (ADRB3 Trp64Arg) polymorphisms using TaqMan allelic discrimination assay or RFLP.

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

“…Furthermore, both CDKN2A and CDKN2B are expressed at high levels in pancreatic islets [23]. It was reported that the SNPs in this region showed a stronger signal as a haplotype [23], but we could not find such a trend in our study (ESM Tables 5 and 6) In our study, the association of TCF7L2 with GDM was not as strong as that reported by the Scandinavian study [17]. This discrepancy may be explained by the difference in the frequency of the rs7903146 risk allele between the Although HHEX was not robustly associated with GDM, it was strongly associated with insulin secretory capacity.…”

“…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.…”

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

“…TCF7L2 polymorphisms modulate blood glucose and insulin secretion and the association of rs7901695 with GDM has previously been described in Caucasians (19). Another TCF7L2 polymorphism (rs7903146), which is in linkage disequilibrium with rs7901695, has been associated with GDM in Danish (23), Australian (21), Greek (5), and Swedish (20) populations.…”

“…The TCF7L2 gene has been associated with T2DM in different populations (19)(20)(21). Common variants in intronic region of TCF7L2 have been identified as strong predictors of T2DM genetic risk (22).…”

Emergence of TCF7L2 as a Most Promising Gene in Predisposition of Diabetes Type II

“…Their results did not support a model of shared major causal pathway in type 2 and type 1 diabetes. On the same lines Shaat et al (2007) investigated whether common genetic variants that have been found associated with T2D or related phenotype would also confer risk for gestational diabetes mellitus. They genotyped SNP rs7903146 of TCF7L2 in 1881 Scandinavian women (cases/control: 649/1232), and found significant difference between cases and control in their genotype frequencies.…”