The I27l Amino Acid Polymorphism of the Hepatic Nuclear Factor-1α Is a Risk Factor for Both Insulin Resistance and the Common Form of Type 2 Diabetes
Resource
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM v.85 pp.2178-2183
Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Journal Volume
v.85
Pages
2178-2183
Date Issued
2000
Date
2000
Author(s)
CHIU, KEN-C
CHUANG, LEE-MING
Abstract
Although mutations of the hepatic nuclear factor-1 (HNF-1) have been found in patients with maturity-onset diabetes of the young, HNF-1 played a very little role on the common form of type 2 diabetes. To investigate the role of I 27L, a common amino acid polymorphism, of HNF-1 on glucose metabolism, insulin sensitivity and -cell function were assessed in a group of healthy, glucose tolerant and normotensive subject using a hyperglycemic clamp. The LL subjects had a lower insulin sensitivity index (ISI, 5.178M/m2/min/pM) than the II or IL subjects (7. 401 M/m2/min/ pM, p=0.018 by Mann-Whitney test). The LL subjects had a higher first phase insulin response (2,267 pM) than the II or IL subjects (1,682 pM, p=0.026 by Mann-Whitney test). After adjusting for covariates, the I27L polymorphism was found to be an independent determinant for ISI ( p=0.004). However, it had no impact on -cell function after adjusting for ISI. By pooling five published data on the I27 L polymorphism, we also found that the L allele was a risk factor for diabetes with a odds ratio of 1.35 (1.11-1.60, 95 % CI). We concluded that the I27L polymorphism is a risk factor for both insulin resistance and type 2 diabetes.
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