Polymorphism in the 5' flanking region of the human insulin gene. Relationships with noninsulin-dependent diabetes mellitus, glucose and insulin concentrations, and diabetes treatment in the Pima Indians.
Polymorphism in the 5' flanking region of the human insulin gene. Relationships with noninsulin-dependent diabetes mellitus, glucose and insulin concentrations, and diabetes treatment in the Pima Indians.
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人胰岛素基因 5 侧翼区域的多态性。
DOI：
10.1172/jci111638
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Permutt,MA
中科院分区：
文献类型：
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作者：
Knowler,WC;Pettitt,DJ;Vasquez,B;Rotwein,PS;Andreone,TL;Permutt,MA
研究了87名年龄至少为35岁的无关皮马印第安人的胰岛素基因侧翼DNA序列变异与非胰岛素依赖型糖尿病（NIDDM）的关系。从外周血白细胞的细胞核中分离DNA并用限制性内切酶消化。在这一地区的变化被发现在皮马印第安人比以前研究的其他种族群体。只发现两类等位基因（1类和3类），类内几乎没有变化。在38名非糖尿病受试者中，47%的受试者和49名NIDDM受试者中，37%的受试者至少发现一个3类等位基因（比值比= 0.65，P = 0.4，比值比的95%置信区间= 0.25至1.67）。然而，纯合性3类等位基因，被发现只在糖尿病患者。在肥胖、空腹或餐后血糖或胰岛素浓度、胰岛素和血糖浓度之间的关系方面，基因型没有差异。携带3类等位基因的糖尿病患者中有61%（11/18）正在接受糖尿病药物治疗，而不携带3类等位基因的糖尿病患者中只有26%（8/31）正在接受糖尿病药物治疗（P = 0.03）。胰岛素基因多态性可能在皮马印第安人NIDDM的发生中没有重要作用，也不影响葡萄糖或胰岛素浓度或它们之间的关系，但3类等位基因，特别是在该人群中纯合子时，可能影响疾病的严重程度，如药物治疗的需要所示。
Variations in DNA sequences flanking the insulin gene were studied in relation to noninsulin-dependent diabetes mellitus (NIDDM) in 87 unrelated Pima Indians at least 35 yr of age. DNA was isolated from nuclei of peripheral blood leukocytes and digested with restriction endonucleases. Less variation in this region was found in Pima Indians than in other racial groups previously studied. Only two classes of alleles (classes 1 and 3) were found, and there was virtually no variation within classes. At least one class 3 allele was found in 47% of the 38 nondiabetic subjects and in 37% of the 49 with NIDDM (odds ratio = 0.65, P = 0.4, 95% confidence interval for the odds ratio = 0.25 to 1.67). Homozygosity for class 3 alleles, however, was found only in diabetics. There were no differences according to genotype in obesity, fasting or postload glucose or insulin concentrations, or in the relationships between insulin and glucose concentrations. 61% (11/18) of the diabetics with a class 3 allele were receiving drug treatment for diabetes compared with only 26% (8/31) of diabetics without a class 3 allele (P = 0.03). The insulin gene polymorphism probably plays no important role in the genesis of NIDDM in Pima Indians, nor does it influence the glucose or insulin concentrations or their relationship to each other, but the class 3 allele, especially when homozygous in this population, may influence the severity of the disease as indicated by need for drug treatment.