Exp Clin Endocrinol Diabetes 2014; 122 - P014
DOI: 10.1055/s-0034-1372031

The insulin-biosynthesis-impairing MADD rs10501320 genetic polymorphism is associated with gestational diabetes in European populations

N Perakakis 1, L Potasso 1, A Lamprinou 1, E Polyzou 2, D Kassanos 2, A Peter 3, R Rasenack 4, G Päth 1, J Seufert 1, K Laubner 1
  • 1University Hospital of Freiburg, Endocrinology/Diabetology, Internal Medicine II, Freiburg, Germany
  • 2University Hospital Attikon, 3 rd Department of Obstetrics and Gynaecology, Athens, Greece
  • 3University Hospital of Tübingen, Endocrinology, Diabetology, Angiology, Nephrology and clinical Chemistry, Internal Medicine IV, Tübingen, Germany
  • 4University Hospital of Freiburg, Department of Obstetrics and Gynaecology, Freiburg, Germany

Objective: Single nucleotide polymorphisms (SNPs) of the MADD gene have been associated with defects in enzymatic conversion of proinsulin to insulin leading to increased fasting glucose levels in humans. In Chinese populations, SNPs of the MADD gene were further associated with type 2 diabetes. The aim of our study was to investigate the influence of two MADD SNPs (rs10501320 and rs10838687) on the development of Gestational Diabetes Mellitus (GDM) in European populations.

Methods: We genotyped the G/C polymorphism, rs10501320 and the T/G polymorphism, rs10838687, of MADD in 90 unrelated women with a history of GDM, 86 women with DM 2 and 144 non-diabetic pregnant women. The prevalence of wild type (CC and GG) and mutated (CG or GG and TG or TT) genotypes were compared among the three groups.

Results: GG and CG genotype (rs10501320) were significantly associated with an increased risk of GDM, compared to the wild-type CC [GG vs. CC, p = 0.01; Odds Ratio (OR)= 3.63; 95% CI = 1.3 – 10.2, GG+CG vs. CC, p = 0.02, OR = 3,145, 95% CI = 1.15 – 8.6], while we did not detect a similar association for the TT and TG genotype (rs10838687) [TT, p = 0.38, OR = 2,13, 95% CI = 0.57 – 7.94/TT+TG, p = 0,259, OR = 2.4, 95% CI = 0.65 – 8.8]. No statistical difference was detected between the GDM and DM 2 groups.

Conclusions: This is the first report of an association between a SNP of the MADD gene (rs10501320) and the development of gestational diabetes in a European Caucasian population. This result indicates that not only insulin resistance but also genetically predisposed dysfunction in insulin synthesis may contribute to the pathogenesis of gestational diabetes.