Type 2 diabetes genetic risk variants and gestational diabetes

a 2019

Type 2 diabetes genetic risk variants and gestational diabetes

BARÁTOVÁ, Beáta, Vendula BARTÁKOVÁ, Beáta BEDNÁRIKOVÁ, Lukáš PÁCAL, Katarína CHALÁSOVÁ et. al.

Basic information

Original name

Type 2 diabetes genetic risk variants and gestational diabetes

Authors

BARÁTOVÁ, Beáta (703 Slovakia), Vendula BARTÁKOVÁ (203 Czech Republic, guarantor, belonging to the institution), Beáta BEDNÁRIKOVÁ (703 Slovakia), Lukáš PÁCAL (203 Czech Republic), Katarína CHALÁSOVÁ (703 Slovakia), Petr JANKŮ (203 Czech Republic) and Kateřina KAŇKOVÁ (203 Czech Republic)

Edition

The 51th Annual Meeting of the Diabetes Pregnancy Study Group (DPSG), 2019

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30214 Obstetrics and gynaecology

Country of publisher

Austria

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14110/19:00108510

Organization unit

Faculty of Medicine

UT WoS

000485303804018

Keywords (in Czech)

gestační diabetes; genetické rizikové skore; single nuklieotidový polymorfismus

Keywords in English

gestational diabetes mellitus; genetic risk score; single nucletoid polymorphism

Abstract

V originále

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 > 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

Links

NV16-28040A, research and development project

Name: Dlouhodobé dopady gestačního diabetes mellitus pro metabolické zdraví žen časně postpartum: význam nových diagnostických kritérií

NV18-01-00046, research and development project

Name: Genetické skóre v predikci rizika diabetu a jeho komplikací

Investor: Ministry of Health of the CR

Citovat

BARÁTOVÁ, Beáta, Vendula BARTÁKOVÁ, Beáta BEDNÁRIKOVÁ, Lukáš PÁCAL, Katarína CHALÁSOVÁ, Petr JANKŮ and Kateřina KAŇKOVÁ. Type 2 diabetes genetic risk variants and gestational diabetes. In The 51th Annual Meeting of the Diabetes Pregnancy Study Group (DPSG). 2019.

@proceedings{1554177,
   author = {Barátová, Beáta and Bartáková, Vendula and Bednáriková, Beáta and Pácal, Lukáš and Chalásová, Katarína and Janků, Petr and Kaňková, Kateřina},
   booktitle = {The 51th Annual Meeting of the Diabetes Pregnancy Study Group (DPSG)},
   keywords = {gestational diabetes mellitus; genetic risk score; single nucletoid polymorphism},
   language = {eng},
   title = {Type 2 diabetes genetic risk variants and gestational diabetes},
   year = {2019}
}

TY  - CONF
ID  - 1554177
AU  - Barátová, Beáta - Bartáková, Vendula - Bednáriková, Beáta - Pácal, Lukáš - Chalásová, Katarína - Janků, Petr - Kaňková, Kateřina
PY  - 2019
TI  - Type 2 diabetes genetic risk variants and gestational diabetes
KW  - gestational diabetes mellitus
KW  - genetic risk score
KW  - single nucletoid polymorphism
N2  - 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 > 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
ER  -

BARÁTOVÁ, Beáta, Vendula BARTÁKOVÁ, Beáta BEDNÁRIKOVÁ, Lukáš PÁCAL, Katarína CHALÁSOVÁ, Petr JANKŮ and Kateřina KAŇKOVÁ. Type 2 diabetes genetic risk variants and gestational diabetes. In \textit{The 51th Annual Meeting of the Diabetes Pregnancy Study Group (DPSG)}. 2019.

Detailed Information on Publication Record