Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus

Abstract Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis m...

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Autores principales:	Rashmi B. Prasad, Karl Kristensen, Anastasia Katsarou, Nael Shaat
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Prediction of diabetes Gestational diabetes Genetics of type 2 diabetes Insulin sensitivity Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/66c6ebd0f03b4af197f11381e55180ef
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spelling	oai:doaj.org-article:66c6ebd0f03b4af197f11381e55180ef2021-11-21T12:04:21ZAssociation of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus10.1186/s12920-021-01123-61755-8794https://doaj.org/article/66c6ebd0f03b4af197f11381e55180ef2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01123-6https://doaj.org/toc/1755-8794Abstract Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.Rashmi B. PrasadKarl KristensenAnastasia KatsarouNael ShaatBMCarticlePrediction of diabetesGestational diabetesGenetics of type 2 diabetesInsulin sensitivityInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Prediction of diabetes Gestational diabetes Genetics of type 2 diabetes Insulin sensitivity Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Prediction of diabetes Gestational diabetes Genetics of type 2 diabetes Insulin sensitivity Internal medicine RC31-1245 Genetics QH426-470 Rashmi B. Prasad Karl Kristensen Anastasia Katsarou Nael Shaat Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
description	Abstract Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.
format	article
author	Rashmi B. Prasad Karl Kristensen Anastasia Katsarou Nael Shaat
author_facet	Rashmi B. Prasad Karl Kristensen Anastasia Katsarou Nael Shaat
author_sort	Rashmi B. Prasad
title	Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
title_short	Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
title_full	Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
title_fullStr	Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
title_full_unstemmed	Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
title_sort	association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
publisher	BMC
publishDate	2021
url	https://doaj.org/article/66c6ebd0f03b4af197f11381e55180ef
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Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus

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