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 DevelopmentReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Klara Rosta, Zahra Al-Aissa, Orsolya Hadarits, Jürgen Harreiter, Ákos Nádasdi, Fanni Kelemen, Dagmar Bancher-Todesca, Zsolt Ko

Fuente: http://plos.srce.hr/



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