Type 2 Diabetes mellitus genetic risk variant T in TCF7L2 rs 7903146 in women is associated with an increased risk for the development of gestational diabetes mellitus (GDM) with necessity of insulin therapy

Objective: Single nucleotide polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene are recognized risk variants for type 2 diabetes (T2D). The aim of this international multicentric analysis was to evaluate the effect of the T risk variant rs7903146 on the development and clinical course of GDM.

Material and methods: We genotyped the TCF7L2 rs7903146 C/T polymorphism in 150 women with a history of GDM (Greek n = 50, German n = 100) and in 160 non-diabetic pregnant women (Greek n = 81, German n = 79). The prevalence of wild-type and risk TT alleles was com

ared in combined and separate country specific analysis. In the GDM group, we evaluated the impact of the mutation on clinical outcomes (therapy with insulin, macrosomy).

Results: The TT variant was associated with an increased risk of GDM (p = 0.021). This association was driven by the Greek cohort (p = 0.002). Women carrying the T variant had a lower BMI (mean 24.86 kg/m² for TT vs. 26.06 kg/m² for CC), and a higher probability of initiation of insulin therapy, both in homozygotes (p = 0.02) and heterozygotes (p = 0.001). No statistically significant effect on the development of macrosomy was detected (p > 0.05).

Conclusions: The TT genotype of TCF7L2 rs7903146 is associated with an increased risk of GDM in Caucasian women, though with different impact on different ethnical populations. The T allele is associated with the risk of therapy with insulin independently from BMI, suggesting an independent effect of the T risk allele on endogenous insulin reserve and the severity of GDM.