Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen
Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still usef...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2161376 |
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| author | Siew Mei Joyce-Tan Shamsul Mohd Zain Munavvar Zubaid Abdul Sattar Nor Azizan Abdullah |
| author_facet | Siew Mei Joyce-Tan Shamsul Mohd Zain Munavvar Zubaid Abdul Sattar Nor Azizan Abdullah |
| author_sort | Siew Mei Joyce-Tan |
| collection | DOAJ |
| description | Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P=0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted P=0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk. |
| format | Article |
| id | doaj-art-9aa27b021e19438c855f377ab8af014b |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-9aa27b021e19438c855f377ab8af014b2025-02-03T01:02:17ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/21613762161376Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of AngiotensinogenSiew Mei Joyce-Tan0Shamsul Mohd Zain1Munavvar Zubaid Abdul Sattar2Nor Azizan Abdullah3Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaSchool of Pharmaceutical Sciences, University Sains Malaysia, 11800 Penang, MalaysiaDepartment of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaGenome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P=0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted P=0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.http://dx.doi.org/10.1155/2016/2161376 |
| spellingShingle | Siew Mei Joyce-Tan Shamsul Mohd Zain Munavvar Zubaid Abdul Sattar Nor Azizan Abdullah Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen Journal of Diabetes Research |
| title | Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen |
| title_full | Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen |
| title_fullStr | Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen |
| title_full_unstemmed | Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen |
| title_short | Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen |
| title_sort | renin angiotensin system gene variants and type 2 diabetes mellitus influence of angiotensinogen |
| url | http://dx.doi.org/10.1155/2016/2161376 |
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