Research article

INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Funda E Orkunoglu-Suer¹ , Heather Gordish-Dressman¹ , Priscilla M Clarkson² , Paul D Thompson³ , Theodore J Angelopoulos⁴ , Paul M Gordon⁵ , Niall M Moyna⁶ , Linda S Pescatello⁷ , Paul S Visich⁸ , Robert F Zoeller⁹ , Brennan Harmon¹ , Richard L Seip³ , Eric P Hoffman¹ and Joseph M Devaney¹

¹Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, 20010, USA

²Department of Exercise Science, University of Massachusetts, Amherst, MA 01003, USA

³Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, CT 06102, USA

⁴Center for Lifestyle Medicine and Department of Health Professions, University of Central Florida, Orlando, FL 32816, USA

⁵Department of Physical Medicine and Rehabilitation, School of Medicine, University of Michigan, Ann Arbor, MI 48108, USA

⁶Department of Sport Science and Health, Dublin City University, Dublin 9, Ireland, UK

⁷Department of Kinesiology, University of Connecticut, Storrs, CT 06269, USA

⁸Human Performance Laboratory, Central Michigan University, Mount Pleasant, MI 48859, USA

⁹Department of Exercise Science and Health Promotion, Florida Atlantic University, Davie, FL 33314, USA

author email corresponding author email

BMC Medical Genetics 2008, 9:117doi:10.1186/1471-2350-9-117

Published:	23 December 2008

Abstract

Background

A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population.

Methods

We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test.

Results

Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm³ vs. GC/CC: n = 181; 268521 ± 5003 mm³; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035).

Conclusion

Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation.