Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
Prasad, Rashmi B. LU ; Kristensen, Karl LU ; Katsarou, Anastasia LU and Shaat, Nael LU
(2021)
In BMC Medical Genomics
14(1).
- 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... (More)
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.
(Less)
- author
- Prasad, Rashmi B.
LU
; Kristensen, Karl
LU
; Katsarou, Anastasia
LU
and Shaat, Nael
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Genetics of type 2 diabetes, Gestational diabetes, Insulin sensitivity, Prediction of diabetes
- in
- BMC Medical Genomics
- volume
- 14
- issue
- 1
- article number
- 274
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:34801028
- scopus:85119509573
- ISSN
- 1755-8794
- DOI
- 10.1186/s12920-021-01123-6
- language
- English
- LU publication?
- yes
- id
- 83eca1c7-8fac-45c1-9648-3f702209f2e5
- date added to LUP
- 2021-12-08 13:25:54
- date last changed
- 2024-06-15 22:16:38
@article{83eca1c7-8fac-45c1-9648-3f702209f2e5,
abstract = {{<p>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.</p>}},
author = {{Prasad, Rashmi B. and Kristensen, Karl and Katsarou, Anastasia and Shaat, Nael}},
issn = {{1755-8794}},
keywords = {{Genetics of type 2 diabetes; Gestational diabetes; Insulin sensitivity; Prediction of diabetes}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Medical Genomics}},
title = {{Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus}},
url = {{http://dx.doi.org/10.1186/s12920-021-01123-6}},
doi = {{10.1186/s12920-021-01123-6}},
volume = {{14}},
year = {{2021}},
}