Association of a Novel Point Mutation (C159G) of the CTLA4 Gene With Type 1 Diabetes in West Africans but not in Chinese

Association of a Novel Point Mutation (C159G) of the CTLA4 Gene With Type 1 Diabetes in West Africans but not in Chinese Douglas Osei-Hyiaman 1 2 , Lifang Hou 1 , Ren Zhiyin 3 , Zhang Zhiming 4 , Haiquin Yu 5 , Abena Agyeiwaa Amankwah 6 and Shoji Harada 7 1 Graduate School of Medicine, University of Tsukuba, Tsukuba city, Ibaraki-ken, Japan 2 Department of Medicine, Division of Endocrinology, Safo Adu Hospital, Kumasi, Ghana 3 Department of Internal Medicine, Taiyuan City Hospital, Shanxi 4 Department of Epidemiology, Shanxi Medical University, Shanxi 5 Department of Internal Medicine, Beicheng Central Hospital, Taiyuan, Shanxi, China 6 School of Medical Sciences, University of Science and Technology, Kumasi, Ghana 7 Graduate School of Medicine, Institute of Community Medicine, University of Tsukuba, Tsukuba city, Ibaraki-ken, Japan Abstract Here, we report on the detection of a novel point mutation of the CTLA4 gene at nucleotide position 159 (C→G) leading to amino acid substitution at position 53 (I→M), as well as its association with type 1 diabetes in two ethnically distinct populations. Subjects included 182 unrelated type 1 diabetes children and 201 control subjects from Ghana, West Africa. The Chinese study population consisted of 350 type 1 diabetic children and 420 healthy control subjects from central China. Polymerase chain reaction–single-strand conformation polymorphism and sequence analysis were used to screen for polymorphisms in the CTLA4 gene. CTLA4 49 (A→G) mutation conferred a risk of type 1 diabetes in the Chinese children (odds ratio 1.78, 95% CI 1.58–2.0), but not in the West African children (1.17, 0.84–1.64). On the other hand, the novel CTLA4 159 (C→G) mutation conferred a risk of type 1 diabetes in the West African children (2.1, 1.54–2.86), but not in the Chinese type 1 diabetic children. The novel CTLA4 gene polymorphism at nucleotide position 159 significantly associated with type 1 diabetes in West Africans, but not in Chinese. On the other hand, the CTLA4 gene polymorphism at nucleotide position 49 significantly associated with type 1 diabetes in Chinese, but not in West Africans. Footnotes Address correspondence and reprint requests to Douglas Osei-Hyiaman, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, (NIH/NIAAA/DICBR/LPS), 12420 Parklawn Dr., MSC-8115, Bethesda, MD 20892-8115. E-mail: dhyiaman{at}mail.nih.gov . D.O.-H. is currently affiliated with the National Institute on Alcohol Abuse