糖尿病遺傳病因學

Genetics of Diabetes Mellitus

吳篤安(Du-An Wu)

《Journal of Medical Sciences》 16卷2期 (1995/10) Pp. 73-82

摘要

糖尿病是糖類代謝異常疾病，可分為四類：胰島素依賴型糖尿病（IDDM）、非胰島素依賴型糖尿病（NIDDM）、妊娠糖尿病、其他型糖尿病。本文就IDDM（第一型糖尿病，舊稱幼年型糖尿病）與NIDDM（第二型糖尿病，舊稱成人型糖尿病）這兩型糖尿病與遺傳的關係，及其致病基因的辨認作一扼要得介紹。目前IDDM已發現18個基因與IDDM有關聯，其中以HLA的位置最重要。MODY在部份家族與GCK或ADA有關連。NIDDM的致病基因尚未確認。有人認為前胰島素，或前胰島素轉換酶等基因和NIDDM的發病有關。亦有許多報告顯示葡萄糖運送蛋白、胰島素受器、胰島素受器基質等基因也可能和NIDDM有關。研究科技的進步帶來新的方向與曙光；只要訓練良好的研究團隊通力合作，加上國際化多中心合作，糖尿病致病基因的確認，指日可待。

關鍵字

糖尿病 ； 遺傳學 ； 複雜型遺傳 ； 關連分析

並列摘要

Diabetes mellitus is a common disorder of glucose homeostasis affecting about 5% of the population. The etiology of hyperglycemia and/or glucose intolerance are not well understood. The relationship between heredity and the development of diabetes has been recognized for years. Mode of inheritance of human diabetes is not easily explained by simple Mendelian model, and was known as a complex disorder. Its heterogeneity in nature, difficulty in obtaining large multi-generation families, inaccuracy of disease diagnosis, obscured pathophysiology confound the linkage analysis. Linkage analysis, allele-sharing method and association study are three main statistic mathods that have been used in most of the human diabetes studies at present. Redefining and subclassifying the disease would render diabetic or glucose intolerant population more homogeneous which may help for the gene (or genes) mapping for diabetes and its related risk factors. Geneticists have been trying to improve statistic methods from two-point to multipoint linage analysis, form affected to quantitative trait analysis. Nummerous genetic markers have been identified with increasing number day by day. This would help to determine a fine map and facilitate the positional cloning. Overall strategies for the identification of diabetes mellitus susceptibility genes are represented by two extremes: the total genomic search and candidate gene approach. Total genomic searing to animal model of diabetes mellitus is an applicable method for human genetic analysis with syntenic regions as candidate gene markers. The elucidation of genetic basis of diabetes mellitus remains an important and achievable goal. International collaborations between multi-center groups will essential.

並列關鍵字

Diabetes Mellitus ； genetics ； linkage analysis ； complex trait