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

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 associ...

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Autores principales: Jeon, Jae-Pil, Shim, Sung-Mi, Nam, Hye-Young, Ryu, Gil-Mi, Hong, Eun-Jung, Kim, Hyung-Lae, Han, Bok-Ghee
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996954/
https://www.ncbi.nlm.nih.gov/pubmed/20624279
http://dx.doi.org/10.1186/1471-2164-11-426
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author Jeon, Jae-Pil
Shim, Sung-Mi
Nam, Hye-Young
Ryu, Gil-Mi
Hong, Eun-Jung
Kim, Hyung-Lae
Han, Bok-Ghee
author_facet Jeon, Jae-Pil
Shim, Sung-Mi
Nam, Hye-Young
Ryu, Gil-Mi
Hong, Eun-Jung
Kim, Hyung-Lae
Han, Bok-Ghee
author_sort Jeon, Jae-Pil
collection PubMed
description 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.
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spelling pubmed-29969542010-12-07 Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus Jeon, Jae-Pil Shim, Sung-Mi Nam, Hye-Young Ryu, Gil-Mi Hong, Eun-Jung Kim, Hyung-Lae Han, Bok-Ghee BMC Genomics Research Article 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. BioMed Central 2010-07-12 /pmc/articles/PMC2996954/ /pubmed/20624279 http://dx.doi.org/10.1186/1471-2164-11-426 Text en Copyright ©2010 Jeon et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jeon, Jae-Pil
Shim, Sung-Mi
Nam, Hye-Young
Ryu, Gil-Mi
Hong, Eun-Jung
Kim, Hyung-Lae
Han, Bok-Ghee
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
title_full Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
title_fullStr Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
title_full_unstemmed Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
title_short Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
title_sort copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996954/
https://www.ncbi.nlm.nih.gov/pubmed/20624279
http://dx.doi.org/10.1186/1471-2164-11-426
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