Background/Aims: Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology-this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors-increased by high protein, glycemic index and energy diets. Methods: Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer-experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6-8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors-energy density, protein content (in grams or in % of total energy intake) and glycemic index-on these four adiposity phenotypes. Results: We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N degrees 2), p = 0.02, beta = -0.2446), and waist change over time (rs7511673 (SNP N degrees 1), p = 0.01, beta = -0.0433 and rs10888390 (SNP N degrees 3), p = 0.04, beta = -0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N degrees 2) was also associated with the risk of being a weight gainer (p(interaction) = 0.01, OR = 1.0526)-the risk of being a weight gainer increased with the percentage of proteins contained in the diet. Conclusion: CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake.
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