A recent study in humans has identified the first genetic link between body mass index (BMI) and carbohydrate metabolism (Nat. Genet. doi:10.1038/ng.2939).

Mario Falchi and his colleagues analyzed DNA arrays for common copy number variants (CNVs) in 651 subjects from 149 Swedish families that had pairs of siblings where one was obese and one was not. By linking the identified CNVs with gene expression data from adipose tissue (to ensure a phenotypic effect of the CNV) and BMI, the authors identified an inverse association between BMI and copy number of the region encoding the salivary amylase gene cluster (AMY1). This cluster encodes a protein called salivary amylase, which initiates carbohydrate digestion in the oral cavity. Quantitative PCR analyses of DNA copy number confirmed this association in another 3,600 European subjects, in which AMY1 copy number could account for 2.47% to 19.86% of the total genetic variation in obesity. Similar results were seen in 2,400 subjects from a Singaporean Chinese case control study, indicating that AMY1 copy number is not a European population–specific genetic risk factor for obesity.

Amounts of plasma salivary amylase in 468 morbidly obese French subjects were linked to copy number and inversely associated with BMI. How these genetic alterations in AMY1 lead to obesity and how to therapeutically exploit this new link between digestive enzyme levels and obesity remain to be explored.