期刊
DIABETOLOGIA
卷 52, 期 10, 页码 2109-2116出版社
SPRINGER
DOI: 10.1007/s00125-009-1391-y
关键词
Age-at-diagnosis; Association study; Autoantibodies; Genetics; PPARG; SLC30A8; Type 1 diabetes; Type 2 diabetes
资金
- Juvenile Diabetes Research Foundation (JDRF) International
- Wellcome Trust [079895]
- National Institute for Health Research Cambridge Biomedical Research Centre
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Allergy and Infectious Disease (NIAID)
- National Human Genome Research Institute (NHGRI)
- National Institute of Child Health and Human Development (NICHD)
- JDRF International
- [U01 DK062418]
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Medical Research Council [G0000934] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10275] Funding Source: researchfish
- MRC [G0000934] Funding Source: UKRI
We used recently confirmed type 2 diabetes gene regions to investigate the genetic relationship between type 1 and type 2 diabetes, in an average of 7,606 type 1 diabetic individuals and 8,218 controls, providing > 80% power to detect effects as small as an OR of 1.11 at a false-positive rate of 0.003. The single nucleotide polymorphisms (SNPs) with the most convincing evidence of association in 12 type 2 diabetes-associated gene regions, PPARG, CDKAL1, HNF1B, WFS1, SLC30A8, CDKN2A-CDKN2B, IGF2BP2, KCNJ11, TCF7L2, FTO, HHEX-IDE and THADA, were analysed in type 1 diabetes cases and controls. PPARG and HHEX-IDE were additionally tested for association in 3,851 type 1 diabetes families. Tests for interaction with HLA class II genotypes, autoantibody status, sex, and age-at-diagnosis of type 1 diabetes were performed with all 12 gene regions. Only PPARG and HHEX-IDE showed any evidence of association with type 1 diabetes cases and controls (p = 0.004 and p = 0.003, respectively; p > 0.05 for other SNPs). The potential association of PPARG was supported by family analyses (p = 0.003; p (combined) = 1.0 x 10(-4)). No SNPs showed evidence of interaction with any covariate (p > 0.05). We found no convincing genetic link between type 1 and type 2 diabetes. An association of PPARG (rs1801282/Pro12Ala) could be consistent with its known function in inflammation. Hence, our results reinforce evidence suggesting that type 1 diabetes is a disease of the immune system, rather than being due to inherited defects in beta cell function or regeneration or insulin resistance.
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