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The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults

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Abstract

Objective

The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population.

Subjects

A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study.

Methods

CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay.

Results

The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3 %), followed by LADA patients (44.2 %) and T2DM patients (38.8 %). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95 % CI 1.168–2.010, P = 0.002) and LADA patients (OR = 1.464, 95 % CI 1.063–2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4 % in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95 % CI 1.1–1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4 % vs. 35.1 % OR = 1.807, 95 % CI 1.125–2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls.

Conclusion

The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level.

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Acknowledgments

This study was supported by the National Science Foundation for Young Scholars of China (81100583), the Natural Science Foundation of China Hunan Province (12JJ4083), the Social Development Supporting Plan Program of the Science and Technology Bureau of Hunan Province (2011SK3242), and the Freedom to Explore Program of Central South University (2011QNZT191).

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

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Authors and Affiliations

  1. Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

    P. Jin, B. Xiang, G. Huang & Z. Zhou

  2. Department of Endorcrinology, The Third Xiangya Hospital, Central South University, Changsha, 410007, Hunan, People’s Republic of China

    P. Jin

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  1. P. Jin
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Correspondence to Z. Zhou.

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Jin, P., Xiang, B., Huang, G. et al. The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults. J Endocrinol Invest 38, 149–154 (2015). https://doi.org/10.1007/s40618-014-0162-x

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