Identification of minimal promoter and genetic variants of kruppel-like factor 11 gene and association analysis with type 2 diabetes in Japanese

Eiji Kuroda, Yukio Horikawa, Mayumi Enya, Naohisa Oda, Eiji Suzuki, Katsumi Iizuka, Jun Takeda

研究成果: ジャーナルへの寄稿学術論文査読

13 被引用数 (Scopus)

抄録

Genetic analysis of the KLF11 gene revealed two rare variants, A347S and T220M, segregating in families with early-onset type 2 diabetes, and one frequent polymorphic Q62R variant significantly associated with type 2 diabetes in Northern Europeans. Furthermore, it has been reported that over-expression of KLF11 has a deleterious effect on insulin promoter activity. Thus, an altered expression level of KLF11 may contribute to the occurrence of type 2 diabetes. To investigate the contribution of KLF11 to type 2 diabetes in Japanese, we surveyed the 5' flanking region of KLF11 by reporter assay and identified the minimal promoter region of the gene. The promoter region from -250 to +162 bp including five Spl binding sites showed basal promoter activity both in MIN6-m9 and HepG2 cells. We also examined the entire region of KLF11 to detect genetic variants. A total of 19 polymorphisms, six of which are novel, were identified, but none of them showed association with the occurrence of type 2 diabetes. Two of the identified polymorphisms, R29Q and S124F, are novel coding variants. Functional analyses of these variants were performed, and similarly reduced effects on transcriptional activities of insulin, catalasel, and the Smad7 gene were found. We conclude that variants of KLF11 are not a major factor in the occurrence of type 2 diabetes in Japanese. The promoter region of KLF11 identified in the present study should be useful in further elucidation of the transcriptional regulation mechanism of the gene and genetic analyses of type 2 diabetes.

本文言語英語
ページ(範囲)275-286
ページ数12
ジャーナルendocrine journal
56
2
DOI
出版ステータス出版済み - 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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