Utilizing Genetic Predisposition Score in Predicting Risk of Type 2 Diabetes Mellitus Incidence: A Community-based Cohort Study on Middle-aged Koreans
Journal of Korean Medical Science 2015³â 30±Ç 8È£ p.1101 ~ p.1109
(Park Hye-Yin) - Seoul National University Bundang Hospital Center for Clinical Preventive Medicine
ÃÖÇüÁø(Choi Hyung-Jin) - Chungbuk National University College of Medicine Department of Internal Medicine
È«À±Ã¶(Hong Yun-Chul) - Seoul National University College of Medicine Department of Preventive Medicine
Abstract
Contribution of genetic predisposition to risk prediction of type 2 diabetes mellitus (T2DM) was investigated using a prospective study in middle-aged adults in Korea. From a community cohort of 6,257 subjects with 8 yr' follow-up, genetic predisposition score with subsets of 3, 18, 36 selected single nucleotide polymorphisms (SNPs) (genetic predisposition score; GPS-3, GPS-18, GPS-36) in association with T2DM were determined, and their effect was evaluated using risk prediction models. Rs5215, rs10811661, and rs2237892 were in significant association with T2DM, and hazard ratios per risk allele score increase were 1.11 (95% confidence intervals: 1.06-1.17), 1.09 (1.01-1.05), 1.04 (1.02-1.07) with GPS-3, GPS-18, GPS-36, respectively. Changes in AUC upon addition of GPS were significant in simple and clinical models, but the significance disappeared in full clinical models with glycated hemoglobin (HbA1c). For net reclassification index (NRI), significant improvement observed in simple (range 5.1%-8.6%) and clinical (3.1%-4.4%) models were no longer significant in the full models. Influence of genetic predisposition in prediction ability of T2DM incidence was no longer significant when HbA1c was added in the models, confirming HbA1c as a strong predictor for T2DM risk. Also, the significant SNPs verified in our subjects warrant further research, e.g. gene-environmental interaction and epigenetic studies.
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Diabetes Mellitus, Genetic Predisposition, Hemoglobin A, Glycosylated
KMID :
0191120150300081101
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Influence of genetic predisposition in prediction ability of T2DM incidence was no longer significant when HbA1c was added in the models, confirming HbA1c as a strong predictor for T2DM risk.