Associations of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride and HDL cholesterol levels in women with type 2 diabetes
Abstract
The apolipoprotein gene cluster (APOA1/C3/A4/A5) was recently associated with triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in non-diabetic population. Little is known whether the variations in these genes affect lipid homeostasis in patients with type 2 diabetes. We examined the associations of 10 polymorphisms at APOA1/C3/A4/A5 gene cluster with blood lipids among 902 diabetic women. A linkage disequilibrium (LD) breakdown was observed between APOA5 and other genes. APOA5 S19W was associated with significantly higher fasting TG levels (P=0.001). Two common haplotypes encompassing four APOA5 polymorphisms (SNP1, SNP2, S19W, and SNP3) were associated with 35.6 mg/dL (haplotype 2212, APOA5*2, P=0.016) and 57.8 mg/dL (haplotype 1121, APOA5*3, P=0.0002) higher fasting TG levels compared with the most common (haplotype 1111, APOA5*1), respectively. Adjustment for age, BMI, and other covariates did not appreciably change such associations. In addition, APOC3 promoter polymorphism -455T/C showed significant associations with fasting TG levels (P=0.006), whereas APOA4 +347T/A showed significant associations with lower levels of HDL-C (P=0.017). Our results indicate that the variability in APOA1/C3/A4/A5 gene cluster may affect TG and HDL levels in women with type 2 diabetes.
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A meta p-value of 2.7×10−10 for rs3135506 reported by Willer et al. in 8,684 subjects, and a meta p-value of 2.4×10−15 for 3,248 subjects in association with triglycerides, represent supportive replication evidence.
“Hence, a meta p-value of 2.7×10−10 for the same polymorphism reported by Willer et al. [99] in a sample of 8,684 subjects, and a meta p-value of 2.4×10−15 for a sample of 3,248 subjects in association with TG represent a supportive replication evidence.”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [99]
The minor allele of rs3135506 (minor allele frequency about 6% in whites) has been repeatedly associated with increased plasma triglyceride concentrations.
“The minor allele of rs3135506 (minor allele frequency (MAF) of about 6% in whites) has been repeatedly associated with increased plasma TG concentrations [96–99].”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [99]
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Kumar, P. (2024) · Innovare Journal of Life Sciences · doi:10.22159/ijls.2024v12.50215
Protein Profiling and Type 2 Diabetes
Sundsten, T. (2008) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
- Authors
- Qi, L., Liu, S., Rifai, N., Hunter, D., & Hu, F. B.
- Affiliations
- Brigham and Women's Hospital (US)
- University of California, Los Angeles (US)
- Harvard University (US)
- Corresponding author
- Qi, Lu
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 192
- Issue
- 1
- Pages
- 204-210
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2025056721
- Cited by
- 67
- References
- 29
- Citations by year
- 2024: 2 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 71981, R01HL071981)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845, DK58845)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, women, triglycerides, HDL cholesterol, haplotypes, linkage disequilibrium, lipid homeostasis, genetic association
- MeSH terms
- Apolipoprotein A-V, Adult, Apolipoproteins A, Diabetes Mellitus, Type 2, Female, Gene Frequency, Haplotypes, Humans, Cholesterol, HDL, Middle Aged, Nurses, Prospective Studies, Triglycerides, Linkage Disequilibrium, Apolipoprotein A-I, Polymorphism, Single Nucleotide, Apolipoprotein C-III
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