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The associations between three genome-wide risk variants for serum C-peptide of T1D and autoantibody-positive T1D risk, and clinical characteristics in Chinese population

Journal of Human Genetics volume 65, pages 297–303 (2020)Cite this article

Subjects

Abstract

Aims

Recent meta-genome-wide association studies identified several genetic variants associated with beta-cell function in type 1 diabetes (T1D). The aim of this study was to investigate the associations between these variants and T1D risk, C-peptide levels, islet-specific autoantibodies, and lipid levels in Chinese Han population.

Methods

A total of 1005 unrelated autoantibody-positive T1D cases and 1417 healthy controls were included, which were genotyped for rs559047, rs9260151, and rs3135002. T1D individuals were measured for both C-peptide and lipid levels. Logistic regression models were used to examine these associations.

Results

We found that rs3135002 A allele showed a genome-wide significant association with T1D risk (OR = 0.22, 95% CI = 0.17–0.30; P = 7.49 × 10−27), and significant heterogeneity of effect size was observed between early-onset and later-onset T1D subgroups (I2 = 80% and P = 0.026). Rs559047 had a nominal association with fasting C-peptide levels in newly diagnosed T1D individuals (P = 0.036). Moreover, rs3135002 A allele was significantly associated with GADA positivity (OR = 0.52, 95% CI = 0.30–0.91, P = 0.02). In addition, nominal correlations were observed with HDL levels for rs559047 (P = 0.042), while LDL levels for rs9260151 (P = 0.032) in T1D individuals.

Conclusions

Our results indicate that there are both similarities and differences for the associations of genetic variants among T1D development, progression, and related autoimmunity, metabolic traits.

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Acknowledgements

The study was supported by grants from the National Natural Science Foundation of China (81670715 and 81270897), Key Program of National Natural Science Foundation of China (81530026), the National Key Project of Research and Development Plan (2016YFC1305000), Jiangsu Province Youth Medical Talents Project (QNRC2016584), the Jiangsu Province Key Science and Technology Development Project (BE2017753), Jiangsu Provincial Special Program of Medical Science (BL2012026), the Natural Science Foundation of Jiangsu province (BK2012486), Jiangsu Government Scholarship for Overseas Studies (JS-2013-260), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. These authors contributed equally: Yingjie Feng, Yuyue Zhang, Yang Chen, Shu Chen

Authors and Affiliations

  1. Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China

    Yingjie Feng, Yuyue Zhang, Yang Chen, Shu Chen, Min Shen, Qi Fu, Yunqiang He, Yuwei Liu, Hsiang-Ting Hsu, Xinyu Xu, Heng Chen, Tao Yang & Kuanfeng Xu

  2. Department of Endocrinology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, 226001, China

    Shu Chen

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  1. Yingjie Feng
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Contributions

KX directed the study design, performed statistical analysis and interpretation of data, and drafted the initial manuscript. YF, YZ and SC were responsible for analysis and interpretation of data. YC, MS, YH, YL, and HTH contributed to collection and selection of samples. QF, XX and HC contributed to Laboratory measurements. TY directed the study design, and critical revision of the manuscript. All the co-authors gave final approval of the version.

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Correspondence to Kuanfeng Xu.

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Feng, Y., Zhang, Y., Chen, Y. et al. The associations between three genome-wide risk variants for serum C-peptide of T1D and autoantibody-positive T1D risk, and clinical characteristics in Chinese population. J Hum Genet 65, 297–303 (2020). https://doi.org/10.1038/s10038-019-0705-2

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