No association of multiple type 2 diabetes loci with type 1 diabetes

作者：Raj S M; Howson J M M; Walker N M; Cooper J D; Smyth D J; Field S F; Stevens H E; Todd J A^*

来源：Diabetologia, 2009, 52(10): 2109-2116.

DOI：10.1007/s00125-009-1391-y

• Age-at-diagnosis
• Association study
• Autoantibodies
• Genetics
• PPARG
• SLC30A8
• Type 1 diabetes
• Type 2 diabetes

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.

• 出版日期2009-10
• 单位河北医科大学