Open Access Research article

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

Kimberly A Skelding1*, Glenn S Gerhard1, Helen Vlachos2, Faith Selzer2, Sheryl F Kelsey2, Xin Chu1, Robert Erdman1, David O Williams3 and Kevin E Kip4

Author Affiliations

1 Weis Center for Research, Geisinger Medical Center, 100 North Academy Avenue, Danville, PA 17822, USA

2 Department of Epidemiology, University of Pittsburgh, PUBHL Pittsburgh, Pittsburgh, PA 15260, USA

3 Division of Cardiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA

4 USF College of Nursing Research Center, University of South Florida, 4202 E. Fowler Avenue Tampa, FL 33620, USA

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BMC Cardiovascular Disorders 2010, 10:46  doi:10.1186/1471-2261-10-46

Published: 29 September 2010

Abstract

Background

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.

Methods and Results

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.

Conclusion

Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.