Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-06

AUTHORS

M. Moritani, K. Nomura, T. Tanahashi, D. Osabe, Y. Fujita, S. Shinohara, Y. Yamaguchi, P. Keshavarz, E. Kudo, N. Nakamura, T. Yoshikawa, E. Ichiishi, Y. Takata, N. Yasui, H. Shiota, K. Kunika, H. Inoue, M. Itakura

ABSTRACT

AIMS/HYPOTHESIS: In order to identify type 2 diabetes disease susceptibility gene(s) in a Japanese population, we applied a region-wide case-control association test to the 20.4 Mb region between D3S1293 and D3S2319 on chromosome 3p24.3-22.1, supported by linkage to type 2 diabetes and its related traits in Japanese and multiple populations. MATERIALS AND METHODS: We performed a two-stage association test using 1,762 Japanese persons with 485 gene-centric, evenly spaced, common single nucleotide polymorphism (SNP) markers with minor allele frequency >0.1. For mouse studies, total RNA was extracted from various organs of BKS.Cg-+Lepr(db)/+Lepr(db) and control mice, and from MIN6, NIH3T3 and C2C12 cell lines. RESULTS: We detected a landmark SNP375 (A/G) (rs2051211, p = 0.000046, odds ratio = 1.33, 95% CI 1.16-1.53) in intron 5 of the endonuclease G-like 1 (ENDOGL1) gene. Systematic dense SNPs approach identified a susceptibility linkage disequilibrium (LD) block of 116.5 kb by |D'|, an LD units map and a critical region of 2.1 kb by r (2) in ENDOGL1. A haplotype-based association test showed that an at-risk haplotype is associated with disease status (p = 0.00001). The expression of ENDOGL1 was rather ubiquitous with relatively abundant expression in the brain and also in a pancreatic islet beta cell line. Mouse Endogl1 expression increased in pancreatic islets of hyperglycaemic BKS.Cg-+Lepr(db)/+Lepr(db) mice compared with that in control mice. CONCLUSIONS/INTERPRETATION: Based on the population genetics, fine mapping of LD block and haplotype analysis, we conclude that ENDOGL1 is a candidate disease-susceptibility gene for type 2 diabetes in a Japanese population. Further analysis in a larger sample size is required to substantiate this conclusion. More... »

PAGES

1218-1227

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-007-0631-2

DOI

http://dx.doi.org/10.1007/s00125-007-0631-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021447229

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17415550


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