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Insulin gene VNTR polymorphisms −2221MspI and −23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis

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Abstract

Aims

A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive.

Methods

We performed a systematic review of work on the INS VNTR −2221MspI and −23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls.

Results

For T1D, the C allele at −2221MspI and the A allele at −23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of −2221MspI and −23HphI on T1D. For −23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of −23HphI on LADA.

Conclusions

Our results support the existence of associations of INS with T1D and LADA.

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Acknowledgments

This work was supported in part by National Natural Science Foundation of China (Grant Nos.: 30901249; 81101267), the Guangdong Natural Science Foundation (Grant Nos.: 10151063201000036; S2011010002526), Guangdong Province Medical Research Foundation (Grant Nos.: A2014374), and Project from Jinan University (Grant Numbers: 21612426, 21615427).

Author contributions

Thanks go to Ammarin Thakkinstian from the section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand; John R. Thompson from the Department of Health Sciences, University of Leicester, UK; Sasivimol Rattanasiri from the section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand, for providing the statistical computing algorithm support. Thanks also go to Leif Groop from the Lund University Diabetes Centre, University Hospital Skåne, Sweden, for providing the detail genotyping data.

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    Authors and Affiliations

    1. Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China

      Na Zhang, Weihuang Huang, Fang Dong, Yang Liu, Baohuan Zhang, Lipeng Jing, Man Wang & Chunxia Jing

    2. Department of Parasitology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China

      Guang Yang

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    Zhang, N., Huang, W., Dong, F. et al. Insulin gene VNTR polymorphisms −2221MspI and −23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis. Acta Diabetol 52, 1143–1155 (2015). https://doi.org/10.1007/s00592-015-0805-1

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