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未来2型糖尿病的遗传预测

Genetic prediction of future type 2 diabetes.

作者信息

Lyssenko Valeriya, Almgren Peter, Anevski Dragi, Orho-Melander Marju, Sjögren Marketa, Saloranta Carola, Tuomi Tiinamaija, Groop Leif

机构信息

Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden.

出版信息

PLoS Med. 2005 Nov 1;2(12):e345. doi: 10.1371/journal.pmed.0020345.

DOI:10.1371/journal.pmed.0020345
PMID:17570749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1274281/
Abstract

BACKGROUND

Type 2 diabetes (T2D) is a multifactorial disease in which environmental triggers interact with genetic variants in the predisposition to the disease. A number of common variants have been associated with T2D but our knowledge of their ability to predict T2D prospectively is limited.

METHODS AND FINDINGS

By using a Cox proportional hazard model, common variants in the PPARG (P12A), CAPN10 (SNP43 and 44), KCNJ11 (E23K), UCP2 (-866G>A), and IRS1 (G972R) genes were studied for their ability to predict T2D in 2,293 individuals participating in the Botnia study in Finland. After a median follow-up of 6 y, 132 (6%) persons developed T2D. The hazard ratio for risk of developing T2D was 1.7 (95% confidence interval [CI] 1.1-2.7) for the PPARG PP genotype, 1.5 (95% CI 1.0-2.2) for the CAPN10 SNP44 TT genotype, and 2.6 (95% CI 1.5-4.5) for the combination of PPARG and CAPN10 risk genotypes. In individuals with fasting plasma glucose > or = 5.6 mmol/l and body mass index > or = 30 kg/m(2), the hazard ratio increased to 21.2 (95% CI 8.7-51.4) for the combination of the PPARG PP and CAPN10 SNP43/44 GG/TT genotypes as compared to those with the low-risk genotypes with normal fasting plasma glucose and body mass index < 30 kg/m(2).

CONCLUSION

We demonstrate in a large prospective study that variants in the PPARG and CAPN10 genes predict future T2D. Genetic testing might become a future approach to identify individuals at risk of developing T2D.

摘要

背景

2型糖尿病（T2D）是一种多因素疾病，环境诱因与疾病易感性中的基因变异相互作用。许多常见变异与T2D相关，但我们对它们前瞻性预测T2D能力的了解有限。

方法与结果

通过使用Cox比例风险模型，研究了PPARG（P12A）、CAPN10（SNP43和44）、KCNJ11（E23K）、UCP2（-866G>A）和IRS1（G972R）基因中的常见变异在芬兰博特尼亚研究中2293名个体中预测T2D的能力。中位随访6年后，132人（6%）患T2D。PPARG的PP基因型发生T2D的风险比为1.7（95%置信区间[CI]1.1-2.7），CAPN10的SNP44的TT基因型为1.5（95%CI 1.0-2.2），PPARG和CAPN10风险基因型组合为2.6（95%CI 1.5-4.5）。在空腹血糖≥5.6 mmol/l且体重指数≥30 kg/m²的个体中，与空腹血糖正常且体重指数<30 kg/m²的低风险基因型个体相比，PPARG的PP和CAPN10的SNP43/44的GG/TT基因型组合的风险比增至21.2（95%CI 8.7-51.4）。

结论

我们在一项大型前瞻性研究中证明，PPARG和CAPN10基因中的变异可预测未来的T2D。基因检测可能成为未来识别有患T2D风险个体的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/c60dcf14568a/pmed.0020345.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/568e7b71913d/pmed.0020345.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/87884d2fe7a4/pmed.0020345.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/c60dcf14568a/pmed.0020345.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/568e7b71913d/pmed.0020345.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/87884d2fe7a4/pmed.0020345.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/1322281/c60dcf14568a/pmed.0020345.g003.jpg

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