The striking similarity between Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes (T2D) in terms of the pathophysiologies and the risk factors has led to the hypothesis that GDM is an early manifestation of T2D, expressed under the stress of pregnancy, and therefore both diseases should share similar susceptibility genes. GDM patients may provide a more homogeneous sample for the genetic causes of the disease than T2D, and therefore make a useful group for the identification of the genes involved. Over 200 GDM affected sib-pairs from 178 families were investigated, with parents available in 40% of cases. Genomic regions from 4 different chromosomes, 6, 8, 14 and 18 were chosen from regions that showed clustering for positive linkage scores in previous linkage studies on T2D and one control region on 13, where no previous positive linkage was reported. A total of 19 microsatellite markers were analysed for linkage to GDM using sib-pair analysis. Subset analyses were performed by ranking sib-pairs on GDM-related variables, e.g. mean BMI of sibs, age at GDM episode, etc. GENEHUNTER was run multiple times, each time including the next highest ranked family in the analysis. This gave a continuous range of scores where increasing or decreasing NPL scores indicated heterogeneity associated with different environmental factors such as age and weight. To evaluate the significance of the subset analyses, the results were compared to 10,000 permutations generated by randomly ranking the sib-pairs. Using the entire dataset, the analysis showed no significant linkage to a disease locus. Positive evidence for linkage was found with the subset analysis on chromosomes 8 and 14, suggesting heterogeneity between sib-pairs in the dataset. Marker D8S1742 on 8p23 showed an NPL score of 3.01 (p=0.001) when age at GDM diagnosis was used as a covariate. Using waist-to-hip ratio (WHR), marker D14S275 on 14q12 showed an NPL score of 2.474 (p=0.006). When adjusted for multiple testing, the results were not statistically significant for linkage to a diabetes disease locus, but gave evidence that GDM and T2D share similar genetic determinants, and defined groups of siblings for follow-up analysis of both types of diabetes.
| Identifer | oai:union.ndltd.org:ADTP/272609 |
| Date | January 2009 |
| Creators | Eltahla, Auda Abdelsalam, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW |
| Publisher | Awarded by:University of New South Wales. Biotechnology & Biomolecular Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Eltahla Auda Abdelsalam., http://unsworks.unsw.edu.au/copyright |
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