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1. 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.

Author

Klara Rosta, Zahra Al-Aissa, Orsolya Hadarits, Jürgen Harreiter, Ákos Nádasdi, Fanni Kelemen, Dagmar Bancher-Todesca, Zsolt Komlósi, László Németh, János Rigó, István Sziller, Anikó Somogyi, Alexandra Kautzky-Willer, and Gábor Firneisz

Subjects
Medicine, Science
Abstract

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

Published
2017
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2. 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

Author

Dagmar Bancher-Todesca, Anikó Somogyi, Zsolt István Komlósi, Zahra Al-Aissa, Fanni Kelemen, István Sziller, Ákos Nádasdi, János Rigó, Alexandra Kautzky-Willer, Jürgen Harreiter, László Németh, Gábor Firneisz, Klara Rosta, and Orsolya Hadarits

Subjects
0301 basic medicine, Oncology, endocrine system diseases, Maternal Health, lcsh:Medicine, Genome-wide association study, Bioinformatics, 0302 clinical medicine, Endocrinology, Pregnancy, Medicine and Health Sciences, lcsh:Science, Cation Transport Proteins, Multidisciplinary, SLC30A8, biology, Obstetrics and Gynecology, Genomics, Gestational diabetes, Female, Genetic Dominance, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Zinc Transporter 8, Genetic Predisposition, Genome Complexity, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, medicine, Genetics, Diabetes Mellitus, Genome-Wide Association Studies, Humans, CDKAL1, Alleles, Receptor, Melatonin, MT2, lcsh:R, Case-control study, Biology and Life Sciences, Computational Biology, nutritional and metabolic diseases, Human Genetics, medicine.disease, Genome Analysis, Introns, Minor allele frequency, Diabetes, Gestational, 030104 developmental biology, Genetic Loci, Metabolic Disorders, Case-Control Studies, Genetics of Disease, biology.protein, Insulin Receptor Substrate Proteins, Women's Health, lcsh:Q, TCF7L2
Abstract

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.

Published
2017

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