Associations of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride and HDL cholesterol levels in women with type 2 diabetes.
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.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, United States. nhlqi@channing.harvard.edu <nhlqi@channing.harvard.edu>
Liu
Simin
S
Rifai
Nader
N
Hunter
David
D
Hu
Frank B
FB
D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009726:Nurses; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood*
C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D014280:Triglycerides; C022205:apolipoprotein A-IV