View : 17 Download: 4

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

Title
Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
Authors
Jeon J.-P.Shim S.-M.Nam H.-Y.Ryu G.-M.Hong E.-J.Kim H.-L.Han B.-G.
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2010
Journal Title
BMC Genomics
ISSN
1471-2164JCR Link
Citation
vol. 11, no. 1
Indexed
SCIE; SCOPUS scopus
Abstract
Background: Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of LEPR gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the LEPR gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the LEPR gene locus in DNA copy number analyses.Results: We identified DNA copy number variations at the LEPR gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between LEPR and LEPROT genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (p = 1.24 × 10-7) and women (p = 9.45 × 10-5), as well as higher total cholesterol levels in men (p = 9.96 × 10-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.Conclusions: This work suggests that a structural variation at the LEPR gene locus is functionally associated with complex metabolic traits and the risk of T2DM. © 2010 Jeon et al; licensee BioMed Central Ltd.
DOI
10.1186/1471-2164-11-426
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus.pdf(312.76 kB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE