https://scholars.lib.ntu.edu.tw/handle/123456789/495638
標題: | Comparison of the impact of the I27L polymorphism of the hepatocyte nuclear factor-1 alpha on estimated and measured beta cell indices | 作者: | Chiu K.C. LEE-MING CHUANG Chu A. Yoon C. Wang M. |
公開日期: | 2003 | 卷: | 148 | 期: | 6 | 起(迄)頁: | 641-647 | 來源出版物: | European Journal of Endocrinology | 摘要: | Objective: We investigated the impact of the I27L polymorphism of the hepatocyte nuclear factor-1alpha gene on measured and estimated beta cell indices. We also examined the conservation of this amino acid among different species. Design and methods: Estimated first and second phase insulin responses (1stPHS and 2ndPHS) were estimated from oral glucose tolerance tests in 78 glucose tolerant subjects. Among these subjects, first and second phase insulin responses (1stIR and 2ndIR) were measured in 60 subjects. The I27L genotypes were determined from genomic DNA. We also reviewed the published peptide sequence data on this polymorphism. Results: The estimated beta cell indices correlated well with the measured indices. Although the impact of this polymorphism was noted in the measured indices (P < 0.01 for 1stIR and P = 0.04 for 2ndIR) from 60 subjects, the differences in the estimated indices were only noted in the extended sample set with 78 subjects (P = 0.05 for 1stPHS and P = 0.04 for 2ndPHS). This polymorphism occurs in the dimerization domain, which is completely conserved within human, rat, mouse and hamster. This amino acid is also conserved in chicken and zebrafish, but not in the frog. This conservation suggests a possible biological importance of this amino acid. Conclusions: By increasing the sample size, we demonstrated the role of the I27L polymorphism in the pathogenesis of type 2 diabetes by using estimated beta cell indices. The conservation among species suggests a possible biological importance of this amino acid. Analysis of the published data confirms a modest role of this polymorphism in type 2 diabetes. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038544699&doi=10.1530%2feje.0.1480641&partnerID=40&md5=94347e3f846e0505838be1069e06593f https://scholars.lib.ntu.edu.tw/handle/123456789/495638 |
ISSN: | 0804-4643 | DOI: | 10.1530/eje.0.1480641 | SDG/關鍵字: | genomic DNA; glucose; insulin; nuclear factor I; amino acid sequence; animal cell; article; chicken; controlled study; correlation analysis; dimerization; female; frog; genetic analysis; genetic conservation; genetic polymorphism; genotype; glucose tolerance; hamster; human; human cell; insulin response; male; mouse; non insulin dependent diabetes mellitus; nonhuman; normal human; nucleotide sequence; oral glucose tolerance test; pancreas islet beta cell; pathogenesis; priority journal; rat; sample size; species difference; zebra fish; Adult; Amino Acid Sequence; Animals; Conserved Sequence; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Female; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Male; Molecular Sequence Data; Nuclear Proteins; Polymorphism, Single Nucleotide; Transcription Factors; Zebrafish Proteins |
顯示於: | 醫學系 |
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