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No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits.

No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits.
No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits.
Background:

The insulin-induced gene 1 (INSIG1) encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose metabolism.

Objective:

We tested for associations between 6 INSIG1 tag single nucleotide polymorphisms (SNPs) (and captured all common variations in INSIG1) and the risk of type 2 diabetes (T2D), obesity, and related traits in 10,567 adults and 1155 adolescents from 5 population-based studies, a T2D case-control study, and a T2D case-series.

Design:

We genotyped tag SNPs and tested them for associations with the risk of T2D or obesity and with body mass index, waist circumference, systolic and diastolic blood pressure, and concentrations of fasting glucose, 2-h oral-glucose-tolerance test glucose, cholesterol, and triglyceride, assuming an additive effect of the minor allele. Dominant effects were tested for the less-frequent SNPs (minor allele frequency <5%). Summary statistics of each study underwent meta-analysis.

Results:

Meta-analyses, which included 1655 T2D cases and 2911 control subjects, showed no association between any of the INSIG1 SNPs and T2D (P > 0.08). Furthermore, none of the SNPs showed an association with obesity in 1666 obese and 5737 nonobese individuals (P > 0.17). In agreement, none of the associations between the SNPs and any of the metabolic traits showed convincing associations in the 7562 adults from 4 population-based studies. Although a few nominally significant associations emerged, none of the associations survived multiple-testing correction. We observed no convincing associations with any of the studied traits in 1155 adolescents.

Conclusion:

Although our study was sufficiently powered to identify small effects, the results suggest that common variation in INSIG1 is unlikely to have a major effect on T2D and obesity risk and related traits in white Europeans.
0002-9165
Szopa, Magdalena
d1ff5aad-5f70-4bae-9b18-2d38cb1d7d5b
Meirhaeghe, Aline
57ef32ef-772e-4950-bdc9-41839ff8e2af
Luan, Jian'an
c6f1b3b4-947f-4ac5-9fef-63dfe2b1bbdd
Moreno, Luis A.
6d282a25-6447-4700-91e5-93f8e8c4a66a
Gonzalez Gross, Marcela
d4a6f6a7-700b-4178-a9c4-06551ae01a6b
Vidal Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Hagen, Rachel
7c51cb48-fc44-4eb7-ab49-77f7af9d1280
Amouyer, Philippe
077ce5cc-a109-4110-adc5-45337e15a658
Wareham, Nicholas J.
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Loos, Ruth J. F.
95946608-9733-4815-a5a5-dad51c62ab91
Szopa, Magdalena
d1ff5aad-5f70-4bae-9b18-2d38cb1d7d5b
Meirhaeghe, Aline
57ef32ef-772e-4950-bdc9-41839ff8e2af
Luan, Jian'an
c6f1b3b4-947f-4ac5-9fef-63dfe2b1bbdd
Moreno, Luis A.
6d282a25-6447-4700-91e5-93f8e8c4a66a
Gonzalez Gross, Marcela
d4a6f6a7-700b-4178-a9c4-06551ae01a6b
Vidal Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Hagen, Rachel
7c51cb48-fc44-4eb7-ab49-77f7af9d1280
Amouyer, Philippe
077ce5cc-a109-4110-adc5-45337e15a658
Wareham, Nicholas J.
bbc18cd9-3512-4ca6-806c-75c9a01e5adf
Loos, Ruth J. F.
95946608-9733-4815-a5a5-dad51c62ab91

Szopa, Magdalena, Meirhaeghe, Aline, Luan, Jian'an, Moreno, Luis A., Gonzalez Gross, Marcela, Vidal Puig, Antonio, Cooper, Cyrus, Hagen, Rachel, Amouyer, Philippe, Wareham, Nicholas J. and Loos, Ruth J. F. (2010) No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits. American Journal of Clinical Nutrition, 92 (1). (doi:10.3945/ajcn.2010.29422).

Record type: Article

Abstract

Background:

The insulin-induced gene 1 (INSIG1) encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose metabolism.

Objective:

We tested for associations between 6 INSIG1 tag single nucleotide polymorphisms (SNPs) (and captured all common variations in INSIG1) and the risk of type 2 diabetes (T2D), obesity, and related traits in 10,567 adults and 1155 adolescents from 5 population-based studies, a T2D case-control study, and a T2D case-series.

Design:

We genotyped tag SNPs and tested them for associations with the risk of T2D or obesity and with body mass index, waist circumference, systolic and diastolic blood pressure, and concentrations of fasting glucose, 2-h oral-glucose-tolerance test glucose, cholesterol, and triglyceride, assuming an additive effect of the minor allele. Dominant effects were tested for the less-frequent SNPs (minor allele frequency <5%). Summary statistics of each study underwent meta-analysis.

Results:

Meta-analyses, which included 1655 T2D cases and 2911 control subjects, showed no association between any of the INSIG1 SNPs and T2D (P > 0.08). Furthermore, none of the SNPs showed an association with obesity in 1666 obese and 5737 nonobese individuals (P > 0.17). In agreement, none of the associations between the SNPs and any of the metabolic traits showed convincing associations in the 7562 adults from 4 population-based studies. Although a few nominally significant associations emerged, none of the associations survived multiple-testing correction. We observed no convincing associations with any of the studied traits in 1155 adolescents.

Conclusion:

Although our study was sufficiently powered to identify small effects, the results suggest that common variation in INSIG1 is unlikely to have a major effect on T2D and obesity risk and related traits in white Europeans.

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More information

Published date: July 2010

Identifiers

Local EPrints ID: 152191
URI: http://eprints.soton.ac.uk/id/eprint/152191
ISSN: 0002-9165
PURE UUID: 4b7e6a38-d1ea-499b-98e7-4ba737f524a5
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 13 May 2010 14:33
Last modified: 18 Mar 2024 02:44

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Contributors

Author: Magdalena Szopa
Author: Aline Meirhaeghe
Author: Jian'an Luan
Author: Luis A. Moreno
Author: Marcela Gonzalez Gross
Author: Antonio Vidal Puig
Author: Cyrus Cooper ORCID iD
Author: Rachel Hagen
Author: Philippe Amouyer
Author: Nicholas J. Wareham
Author: Ruth J. F. Loos

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