Association of a Novel Point Mutation (C159G) of the CTLA4 Gene With Type 1 Diabetes in West Africans but not in Chinese
- Douglas Osei-Hyiaman12,
- Lifang Hou1,
- Ren Zhiyin3,
- Zhang Zhiming4,
- Haiquin Yu5,
- Abena Agyeiwaa Amankwah6 and
- Shoji Harada7
- 1Graduate School of Medicine, University of Tsukuba, Tsukuba city, Ibaraki-ken, Japan
- 2Department of Medicine, Division of Endocrinology, Safo Adu Hospital, Kumasi, Ghana
- 3Department of Internal Medicine, Taiyuan City Hospital, Shanxi
- 4Department of Epidemiology, Shanxi Medical University, Shanxi
- 5Department of Internal Medicine, Beicheng Central Hospital, Taiyuan, Shanxi, China
- 6School of Medical Sciences, University of Science and Technology, Kumasi, Ghana
- 7Graduate 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
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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 and Alcoholism, National Institutes of Health, Bethesda, Maryland. L.H. is currently affiliated with the Sidney Kimmel Cancer Center, San Diego, California.
Received for publication 2 November 2000 and accepted in revised form 8 June 2001.
APC, antigen-presenting cell; ICA, islet cell antibody; OR, odds ratio; PCR, polymerase chain reaction; SSCP, single-strand conformation polymorphism.
