Type 2 diabetes genetic risk variants and gestational diabetes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00108510" target="_blank" >RIV/00216224:14110/19:00108510 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Type 2 diabetes genetic risk variants and gestational diabetes

Popis výsledku v původním jazyce

Objective: Gestational diabetes (GDM) is defined as any degree of glucose intolerance first diagnosed in pregnancy. Glucose intolerance usually disappears after delivery, however GDM increases the risk of developing type 2 diabetes (T2DM) in future life. Considering similar etiopathogenesis of GDM and T2DM (decrease of insulin sensitivity as a common pattern) we can assume shared genetic risk factors. In the present study we focused on selected SNPs associated with T2DM in genome-wide association studies (GWAS). The aim was to compare genotype and allele frequencies of 14 SNPs (genetic variants in the following loci: FTO, JAZF1, MAEA, CDKN2A/B, TLE4, TP53INP1, KCNQ1, ARAP1, NOTCH2, PPARG, WFS1, SLC30A8, KCNJ11, MTNR1B) between healthy women and women with GDM. Weighted genetic risk score (GRS) was calculated to study risk variants as a quantitative trait. We also studied relationship between SNPs and selected clinical phenotypes such as BMI, insulin therapy and peripartal risk caused by GDM according to the Czech Gynaecological and Obstetrical Society (CGOS) criteria. Methods: A case-control study included 269 women, 209 had GDM and 60 had normal pregnancy. GDM diagnosis was based on the result of routine mid-gestational GDM screening using oral glucose tolerance test (oGTT) with 75 g of glucose between 24-28th week of pregnancy. Genetic variants were selected from established GRS composed of 65 SNPs that is associated with 3-times higher risk of T2DM. All selected SNPs had OR &gt; 1.1 in the original study. Detection of SNPs was performed by quantitative PCR based methodology (TaqMan Genotyping Assays). Results: Comparison of allele and genotype frequencies of selected polymorphisms between women with and without GDM showed significant difference in FTO variant rs9936385 (allele frequency, P = 0.024 and genotype frequency, P = 0.054). The difference was also confirmed in comparison of women with BMI lower and higher than 25 kg/m2 (genotype frequency, P = 0.00249; allele frequency, P = 0.02). Another significant difference was shown in genotype frequencies of JAZF1 polymorphism rs849135 within GDM group between insulin-treated and non-insulin-treated women (P = 0.036). Genotype frequencies of JAZF1 rs849135 and allele and genotype frequencies of CDKAL1 rs7756992 differed between women with low and a high risk according to the CGOS criteria (P = 0.037; 0.0211 and 0.012). GRS did not differ between women with and without GDM. Conclusions: Founded association of FTO gene with GDM is in agreement with results of previous association studies including GWAS, which linked FTO gene to obesity. It confirms that obesity is a major driver of GDM development. JAF1 variant is usually linked to insulin secretion and in our study, it was associated with insulin therapy requirement. Acknowledgement: Czech Health Research Council grant NV18-01-00046

Název v anglickém jazyce

Type 2 diabetes genetic risk variants and gestational diabetes

Popis výsledku anglicky

Objective: Gestational diabetes (GDM) is defined as any degree of glucose intolerance first diagnosed in pregnancy. Glucose intolerance usually disappears after delivery, however GDM increases the risk of developing type 2 diabetes (T2DM) in future life. Considering similar etiopathogenesis of GDM and T2DM (decrease of insulin sensitivity as a common pattern) we can assume shared genetic risk factors. In the present study we focused on selected SNPs associated with T2DM in genome-wide association studies (GWAS). The aim was to compare genotype and allele frequencies of 14 SNPs (genetic variants in the following loci: FTO, JAZF1, MAEA, CDKN2A/B, TLE4, TP53INP1, KCNQ1, ARAP1, NOTCH2, PPARG, WFS1, SLC30A8, KCNJ11, MTNR1B) between healthy women and women with GDM. Weighted genetic risk score (GRS) was calculated to study risk variants as a quantitative trait. We also studied relationship between SNPs and selected clinical phenotypes such as BMI, insulin therapy and peripartal risk caused by GDM according to the Czech Gynaecological and Obstetrical Society (CGOS) criteria. Methods: A case-control study included 269 women, 209 had GDM and 60 had normal pregnancy. GDM diagnosis was based on the result of routine mid-gestational GDM screening using oral glucose tolerance test (oGTT) with 75 g of glucose between 24-28th week of pregnancy. Genetic variants were selected from established GRS composed of 65 SNPs that is associated with 3-times higher risk of T2DM. All selected SNPs had OR &gt; 1.1 in the original study. Detection of SNPs was performed by quantitative PCR based methodology (TaqMan Genotyping Assays). Results: Comparison of allele and genotype frequencies of selected polymorphisms between women with and without GDM showed significant difference in FTO variant rs9936385 (allele frequency, P = 0.024 and genotype frequency, P = 0.054). The difference was also confirmed in comparison of women with BMI lower and higher than 25 kg/m2 (genotype frequency, P = 0.00249; allele frequency, P = 0.02). Another significant difference was shown in genotype frequencies of JAZF1 polymorphism rs849135 within GDM group between insulin-treated and non-insulin-treated women (P = 0.036). Genotype frequencies of JAZF1 rs849135 and allele and genotype frequencies of CDKAL1 rs7756992 differed between women with low and a high risk according to the CGOS criteria (P = 0.037; 0.0211 and 0.012). GRS did not differ between women with and without GDM. Conclusions: Founded association of FTO gene with GDM is in agreement with results of previous association studies including GWAS, which linked FTO gene to obesity. It confirms that obesity is a major driver of GDM development. JAF1 variant is usually linked to insulin secretion and in our study, it was associated with insulin therapy requirement. Acknowledgement: Czech Health Research Council grant NV18-01-00046

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů