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Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS:...

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Autores principales: Rosta, Klara, Al-Aissa, Zahra, Hadarits, Orsolya, Harreiter, Jürgen, Nádasdi, Ákos, Kelemen, Fanni, Bancher-Todesca, Dagmar, Komlósi, Zsolt, Németh, László, Rigó, János, Sziller, István, Somogyi, Anikó, Kautzky-Willer, Alexandra, Firneisz, Gábor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224877/
https://www.ncbi.nlm.nih.gov/pubmed/28072873
http://dx.doi.org/10.1371/journal.pone.0169781
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author Rosta, Klara
Al-Aissa, Zahra
Hadarits, Orsolya
Harreiter, Jürgen
Nádasdi, Ákos
Kelemen, Fanni
Bancher-Todesca, Dagmar
Komlósi, Zsolt
Németh, László
Rigó, János
Sziller, István
Somogyi, Anikó
Kautzky-Willer, Alexandra
Firneisz, Gábor
author_facet Rosta, Klara
Al-Aissa, Zahra
Hadarits, Orsolya
Harreiter, Jürgen
Nádasdi, Ákos
Kelemen, Fanni
Bancher-Todesca, Dagmar
Komlósi, Zsolt
Németh, László
Rigó, János
Sziller, István
Somogyi, Anikó
Kautzky-Willer, Alexandra
Firneisz, Gábor
author_sort Rosta, Klara
collection PubMed
description CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria.
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spelling pubmed-52248772017-01-31 Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development Rosta, Klara Al-Aissa, Zahra Hadarits, Orsolya Harreiter, Jürgen Nádasdi, Ákos Kelemen, Fanni Bancher-Todesca, Dagmar Komlósi, Zsolt Németh, László Rigó, János Sziller, István Somogyi, Anikó Kautzky-Willer, Alexandra Firneisz, Gábor PLoS One Research Article CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria. Public Library of Science 2017-01-10 /pmc/articles/PMC5224877/ /pubmed/28072873 http://dx.doi.org/10.1371/journal.pone.0169781 Text en © 2017 Rosta et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rosta, Klara
Al-Aissa, Zahra
Hadarits, Orsolya
Harreiter, Jürgen
Nádasdi, Ákos
Kelemen, Fanni
Bancher-Todesca, Dagmar
Komlósi, Zsolt
Németh, László
Rigó, János
Sziller, István
Somogyi, Anikó
Kautzky-Willer, Alexandra
Firneisz, Gábor
Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title_full Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title_fullStr Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title_full_unstemmed Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title_short Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
title_sort association study with 77 snps confirms the robust role for the rs10830963/g of mtnr1b variant and identifies two novel associations in gestational diabetes mellitus development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224877/
https://www.ncbi.nlm.nih.gov/pubmed/28072873
http://dx.doi.org/10.1371/journal.pone.0169781
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