Cargando…
Relevance of polymorphisms in MC4R and BDNF in short normal stature
BACKGROUND: Variation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this co...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106737/ https://www.ncbi.nlm.nih.gov/pubmed/30134862 http://dx.doi.org/10.1186/s12887-018-1245-1 |
_version_ | 1783349837445464064 |
---|---|
author | Herrfurth, Nikolas Volckmar, Anna-Lena Peters, Triinu Kleinau, Gunnar Müller, Anne Cetindag, Cigdem Schonnop, Laura Föcker, Manuel Dempfle, Astrid Wudy, Stefan A. Grant, Struan F. A. Reinehr, Thomas Cousminer, Diana L. Hebebrand, Johannes Biebermann, Heike Hinney, Anke |
author_facet | Herrfurth, Nikolas Volckmar, Anna-Lena Peters, Triinu Kleinau, Gunnar Müller, Anne Cetindag, Cigdem Schonnop, Laura Föcker, Manuel Dempfle, Astrid Wudy, Stefan A. Grant, Struan F. A. Reinehr, Thomas Cousminer, Diana L. Hebebrand, Johannes Biebermann, Heike Hinney, Anke |
author_sort | Herrfurth, Nikolas |
collection | PubMed |
description | BACKGROUND: Variation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this common condition. METHODS: We analyzed the coding regions of LEP, MC4R, MRAP2 and BDNF in 185 children with SNS (height < 5th percentile) to search for non-synonymous and frameshift variants. For association studies (two-sided χ(2)-tests) population-based data sets (ExAC, EVS and KORA) were used. Cyclic AMP accumulation, cell surface expression, central expression and MAP kinase activation were assayed in vitro to determine the functional implications of identified variants. RESULTS: We detected eleven variants predicted to be protein-altering, four in MC4R, four in BDNF, and three in MRAP2. No variants were found in LEP. In vitro analysis implied reduced function for the MC4R variant p.Met215Ile. Loss-of-function is contrary to expectations based on obesity studies, and thus does not support that this variant is relevant for SNS. The minor SNP alleles at MC4R p.Val103Ile and BDNF p.Val66Met were nominally associated with SNS. CONCLUSION: Taken together, although genes of the leptinergic-melanocortinergic system are important for normal growth, our data do not support the involvement of rare mutations in LEP, MC4R, MRAP2 or BDNF in short normal stature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1245-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6106737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61067372018-08-29 Relevance of polymorphisms in MC4R and BDNF in short normal stature Herrfurth, Nikolas Volckmar, Anna-Lena Peters, Triinu Kleinau, Gunnar Müller, Anne Cetindag, Cigdem Schonnop, Laura Föcker, Manuel Dempfle, Astrid Wudy, Stefan A. Grant, Struan F. A. Reinehr, Thomas Cousminer, Diana L. Hebebrand, Johannes Biebermann, Heike Hinney, Anke BMC Pediatr Research Article BACKGROUND: Variation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this common condition. METHODS: We analyzed the coding regions of LEP, MC4R, MRAP2 and BDNF in 185 children with SNS (height < 5th percentile) to search for non-synonymous and frameshift variants. For association studies (two-sided χ(2)-tests) population-based data sets (ExAC, EVS and KORA) were used. Cyclic AMP accumulation, cell surface expression, central expression and MAP kinase activation were assayed in vitro to determine the functional implications of identified variants. RESULTS: We detected eleven variants predicted to be protein-altering, four in MC4R, four in BDNF, and three in MRAP2. No variants were found in LEP. In vitro analysis implied reduced function for the MC4R variant p.Met215Ile. Loss-of-function is contrary to expectations based on obesity studies, and thus does not support that this variant is relevant for SNS. The minor SNP alleles at MC4R p.Val103Ile and BDNF p.Val66Met were nominally associated with SNS. CONCLUSION: Taken together, although genes of the leptinergic-melanocortinergic system are important for normal growth, our data do not support the involvement of rare mutations in LEP, MC4R, MRAP2 or BDNF in short normal stature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1245-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-22 /pmc/articles/PMC6106737/ /pubmed/30134862 http://dx.doi.org/10.1186/s12887-018-1245-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Herrfurth, Nikolas Volckmar, Anna-Lena Peters, Triinu Kleinau, Gunnar Müller, Anne Cetindag, Cigdem Schonnop, Laura Föcker, Manuel Dempfle, Astrid Wudy, Stefan A. Grant, Struan F. A. Reinehr, Thomas Cousminer, Diana L. Hebebrand, Johannes Biebermann, Heike Hinney, Anke Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title | Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title_full | Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title_fullStr | Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title_full_unstemmed | Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title_short | Relevance of polymorphisms in MC4R and BDNF in short normal stature |
title_sort | relevance of polymorphisms in mc4r and bdnf in short normal stature |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106737/ https://www.ncbi.nlm.nih.gov/pubmed/30134862 http://dx.doi.org/10.1186/s12887-018-1245-1 |
work_keys_str_mv | AT herrfurthnikolas relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT volckmarannalena relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT peterstriinu relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT kleinaugunnar relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT mulleranne relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT cetindagcigdem relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT schonnoplaura relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT fockermanuel relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT dempfleastrid relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT wudystefana relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT grantstruanfa relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT reinehrthomas relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT cousminerdianal relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT hebebrandjohannes relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT biebermannheike relevanceofpolymorphismsinmc4randbdnfinshortnormalstature AT hinneyanke relevanceofpolymorphismsinmc4randbdnfinshortnormalstature |