Variants in PPARγ may increase risk for gestational diabetes
MedWire News: Two variants in the peroxisome proliferator-activated receptor-γ gene (PPARγ) are associated with increased risk for gestational diabetes mellitus (GDM), report French researchers.
"The protective role of the Ala allele in the Pro12Ala polymorphism of PPARγ on Type 2 diabetes has been well established, but not confirmed in the context of pregnancy, for GDM, a known predictor of later Type 2 diabetes onset," write Barbara Heude (Institut National de la Santé et de la Recherche Médicale, Villejuif, France) and colleagues.
Heude and team genotyped 1708 women from the EDEN (study of pre- and postnatal determinants of children's growth and development) mother-child cohort for the PPARγ Pro12Ala polymorphism, and another variant in the same gene, C1431T, which is linked with body weight and potentially diabetes risk.
The EDEN study enrolled 2002 women during pregnancy and then followed-up their children until the age of 5 years. The 1708 women included in this study had body mass index (BMI) measurements taken before their pregnancy, available information on GDM, and had at least one of the two polymorphisms genotyped.
The team found that mothers homozygous for the Ala allele of Pro12Ala had a significantly higher prevalence of obesity (BMI over 30 kg/m2) than Pro allele carriers at 35% versus 9%. However, no Ala/Ala genotype mothers had GDM.
T allele homozygote mothers for the C1431T polymorphism were more likely to be obese than C allele carriers, with a prevalence of 24% versus 9%. They also had a significant three times greater prevalence of GDM than C allele carriers, at 18% versus 6%.
Mothers with GDM were significantly more likely to have the Pro-T haplotype than mothers who did not experience GDM.
When compared with those with the Pro-C haplotype, women with the Pro-T haplotype were a significant 89% more likely to have experienced GDM. Conversely, the Ala-C haplotype was associated with a nonsignificant 78% reduction in risk for GDM compared with the Pro-C haplotype.
"Our study suggests for the first time that genetic variations in the PPARγ gene could play a role in the susceptibility to develop GDM," write Heude and co-authors in the Journal of Clinical Endocrinology and Metabolism.
"Despite the strong linkage disequilibrium between the two polymorphisms Pro12Ala and C1431T of the PPARγ gene, the variants of both were associated with GDM in opposite direction, with the Ala-C haplotype being protective and the Pro-T haplotype a risk factor."
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By Helen Albert