期刊
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
卷 38, 期 2, 页码 149-154出版社
SPRINGER
DOI: 10.1007/s40618-014-0162-x
关键词
Latent autoimmune diabetes in adults; Cytotoxic T-lymphocyte antigen-4; Polymorphism; Type 1 diabetes; Glutamic acid decarboxylase; Autoantibodies
资金
- National Science Foundation for Young Scholars of China [81100583]
- Natural Science Foundation of China Hunan Province [12JJ4083]
- Social Development Supporting Plan Program of the Science and Technology Bureau of Hunan Province [2011SK3242]
- Freedom to Explore Program of Central South University [2011QNZT191]
Objective The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA4) + 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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