Increased risk for gestational diabetes mellitus associated with insulin receptor and insulin-like growth factor II restriction fragment length polymorphisms
✍ Scribed by Carole Ober; Kun-San Xiang; Ronald A. Thisted; Kelly Andrew Indovina; Candace J. Wason; Sharon Dooley; D. C. Rao
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 720 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0741-0395
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✦ Synopsis
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. We have examined restriction fragment length polymorphisms (RFLPs) near "candidate diabetogenic genes" as one approach to identify molecular markers for GDM genes. Genotypes for insulin hypervariable region (HVR), insulin-like growth factor I1 (IGF2), insulin receptor (INSR), and glucose transporter (GLUTI) RFLPs were studied in 96 GDM and 164 control subjects, matched to GDM for race, age, and gravidity. Logistic regression analysis was used to explore the relationship between genotypes at these candidate gene loci and GDM, while adjusting for the effects of potential confounding variables. Among black subjects, the INSR allele 1 (P = 0.001) and interactions between INSR allele 1 with body mass index (BMI) ( P = 0.002) and history of DM in subject's mother (P = 0.004) contributed significantly to GDM risk. Among Caucasian subjects, a similar relationship between the INSR allele l (P = 0.007) and INSR allele 1-BMI interactions ( P = 0.01 1) on GDM risk were observed. In Caucasians, an additional significant risk factor was determined by an INSR allele l-IGF2 allele 2 interaction ( P = 0.018). No risk factors were identified in Hispanic subjects. These data continue to support the hypothesis that GDM is a heterogeneous disorder with respect to phenotypic and genotypic features. Furthermore, our data suggest that risk for GDM in black and Caucasian subjects is not due to obesity per se but to interactions between obesity and INSR alleles. In Caucasian women, INSR