Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent

Weis Center for Research, Geisinger Medical Center, Danville, PA 17822, USA.
BMC Cardiovascular Disorders (Impact Factor: 1.88). 09/2010; 10(1):46. DOI: 10.1186/1471-2261-10-46
Source: PubMed


The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP) near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD) related phenotypes.
Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI) in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD) was significantly higher in older men (≥65 years) who were either homozygous or carriers of the obesity/lipid risk allele ("C") compared to non-carriers (odds ratio 3.4, p = 0.013) using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65) women (odds ratio 3.4, p = 0.013). The INSIG2 SNP was not associated with BMI, nor with other clinical variables.
Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.

Download full-text


Available from: Xin Chu
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To construct the recombinant plasmid containing human insulin induced gene-2 (Insig-2) promoter luciferase reporter, and determine its transcriptional activity. Methods: The promoter fragment at a length of 1 389 bp upstream at transcription site of insig-2 gene was amplified by PCR from human genomic DNA and inserted into vector pGL3-basic. The constructed recombinant plasmid pGL3-Insig-2 and internal reference plasmid pRL-TK were transiently co-transfected to HEK293, HepG2 and 3T3-L1 cells, and determined for Insig-2 promoter activity by dual-luciferase reporter assay. Results: Restriction analysis and sequencing proved that recombinant plasmid pGL3-Insig-2 was constructed correctly. The recombinant plasmid showed promoter activity in HEK293, HepG2 and 3T3-L1 cells, which were 28, 40 and 214 times of those in negative control group(empty vector pGL3-basic) and 2.6, 5.5 and 30 times of those in positive control group (pGL3-SV40), respectively. Conclusion: Recombinant plasmid containing Insig-2 promoter luciferase reporter was successfully constructed, which laid a foundation of further study on the gene.
    No preview · Article · Apr 2013 · Chinese Journal of Biologicals
  • [Show abstract] [Hide abstract]
    ABSTRACT: A genome-wide association study showed that the tagging single nucleotide polymorphism (SNP) rs7566605 in the insulin-induced gene 2 (INSIG2) was associated with obesity. Attempts to replicate this result in different populations have produced inconsistent findings. We aimed to study the association between the rs7566605 SNP with obesity and other metabolic parameters in Malaysian Malays. Anthropometric and obesity-related metabolic parameters and DNA samples were collected. We genotyped the rs7566605 polymorphism in 672 subjects using real-time polymerase chain reaction. No significant associations were found between the rs7566605 tagging SNP of INSIG2 with obesity or other metabolic parameters in the Malaysian Malay population. The INSIG2 rs7566605 SNP may not play a role in the development of obesity-related metabolic traits in Malaysian Malays.
    No preview · Article · Jul 2014 · Genetics and molecular research: GMR