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29-06-2011 | Cardiometabolic | Article

Genetic study suggests that low body weight may not reduce heart disease, diabetes risk


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MedWire News: UK researchers have identified a gene variant that is linked to low body fat and impaired metabolism.

"The body-fat-decreasing allele near the insulin receptor substrate 1 gene (IRS1) is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease, and decreased adiponectin levels," say Ruth Loos (Institute of Metabolic Science, Cambridge, UK) and colleagues.

These findings "provide new insights into adiposity and insulin resistance," they comment in journal Nature Genetics.

To identify common loci associated with adiposity, the research group first conducted a meta-analysis of 15 genome-wide association studies, including over 36,000 individuals, and followed up the most significant independent loci in 39,576 further individuals.

The team found that a single nucleotide polymorphism (SNP) near IRS1 was significantly associated with body fat percentage. Specifically, each copy of the major allele was associated with a 0.16% lower percentage body fat. This association was strongest in men, at 0.20%, compared with 0.06% in women.

Further analyses revealed that the SNP was also associated with higher triglycerides and lower high-density lipoprotein cholesterol levels, and with increased insulin resistance in both genders.

Of note, there were no associations between the SNP and body mass index (BMI).

"As BMI represents both fat and lean mass, whereas body fat percentage is a measure of the relative proportion of these two tissues, our observation suggests that the locus near IRS1 specifically influences adiposity, or alternatively, influences fat mass and lean body mass in opposite directions," explain Loos et al.

When the researchers examined whether the observed correlations could be caused by joint associations with body fat distribution, they found that the variant allele was significantly associated with reduced subcutaneous fat in men, but not in women, whereas no association was observed with visceral fat in either men or women.

The authors note that the SNP near IRS1 has previously been associated with an increased risk for Type 2 diabetes and coronary artery disease.

"Our data thus suggest that the locus near IRS1 may associate with a reduced storage of subcutaneous fat in men, which could contribute to the associations of this locus with insulin resistance and dyslipidemia by leading to an ectopic deposition of lipids," say the researchers.

They add that the gender differences observed in their study requires further investigation.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Nikki Withers

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