Interaction between SREBP‐1a and APOB polymorphisms influences total and low‐density lipoprotein cholesterol levels in patients with coronary artery disease

Abstract

In this study, we examined the insertion/deletion (Ins/Del) and XbaI polymorphisms of the apolipoprotein B (APOB) gene and the -36delG polymorphism in the sterol regulatory element binding protein-1a (SREBP-1a) gene in 298 patients with non-diabetic angiographically assessed coronary artery disease (CAD), and 188 healthy controls, from a Brazilian population of European descent. Del/X+ haplotype carriers had higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in patients (TC, p = 0.05; LDL-C, p = 0.049) and controls (TC, p = 0.004; LDL-C, p = 0.013). No association was detected between the SREBP-1a-36delG polymorphism and lipid levels, but a significant interaction effect between APOB and SREBP-1a polymorphisms was observed in the patient sample on TC (p = 0.005) and on LDL-C (p = 0.019) levels. Carriers of the APOB Del/X+ haplotype and SREBP-1a G-G- genotype showed the highest levels of these lipid parameters. This effect of interaction was not observed in the control sample. Despite the associations with lipids, these polymorphisms were not associated with CAD risk or severity in this sample.

Genetic Markers Associated to Dyslipidemia in HIV‐Infected Individuals on HAART

“…The homozygotes for the alleles T and Del had higher levels of these lipids than individuals heterozygous for both alleles, who had intermediate levels; this result is compatible with a co-dominant effect of these polymorphisms. These results are in agreement with published data showing that the Del and T alleles are associated with increased levels of TC and/or LDL-C in different populations with distinct diseases [9, 35–37]. However, Xu et al and Ye et al found no association of the polymorphism in the signal peptide of the gene with TC and LDL-C levels in the Finnish and Chinese populations, respectively [38, 39].…”

Atorvastatin effects on SREBF1a and SCAP gene expression in mononuclear cells and its relation with lowering-lipids response

“…These results are similar to that found in other populations (SREBF1: 51%-63%; SCAP: 43%-53%) [16,18,19,32,33].…”

Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

“…23 Considering this finding and the strong LD in the region around SREBF1 on 17p11.2, it is possible that the association observed with the RAI1 marker is actually picking up signal from a SREBF1 variant, or vice versa. In dbSNP (http:// www.ncbi.nlm.nih.gov/projects/SNP/) and the scientific literature, several SNPs have been reported to change the amino acid composition of SREBP1 or to influence the level of cholesterol synthesis, [24][25][26] but none of these SNPs are deposited in HapMap and we have therefore not been able to conclude on their LD to the associated SNPs of the present study. The SREBF2 gene is located on chromosome 22q13.2.…”