Mannose-Binding Lectin Gene Variation and Cardiovascular Disease in Canadian Inuit (Technical Briefs‪)‬

Canadian Inuit have an age-adjusted mortality from cardiovascular disease that is ~40% lower than the rest of Canada (1). This might result from the protective influence of certain environmental factors, such as the consumption of Arctic fish (1) or of certain genetic factors. For example, the thermolabile variant of the MTHFR gene, which encodes methylenetetrahydrofolate reductase, is one-sixth as prevalent in Inuit than in subjects of European origin (2). However, there are some inconsistent genetic findings in these people. For example, genetic variants that are associated with an increased risk of cardiovascular disease, such as the E4 allele of the APOE gene and the T235 allele of the AGT gene, are significantly more prevalent in Inuit than in whites (3). The resolution of such inconsistencies may come from the fact that several genes likely determine susceptibility to cardiovascular disease (4). It will thus be necessary to evaluate newer genetic determinants of cardiovascular disease risk in the Inuit. One possible new genetic determinant for cardiovascular risk is the common coding sequence variation in the MBL gene, which encodes mannose-binding lectin (MBL) (5). MBL is an innate immune defense protein that binds mannose and other sugars on the surface of a variety of infectious agents, thereby facilitating phagocytosis and activation of the complement cascade (6, 7). MBL likely modulates the severity of infection with Chlamydia pneumoniae (6, 7), a pathogen linked by several lines of experimentation to the initiation and propagation of atherosclerosis (8). This might explain the association of genetic variation in MBL with severe atherosclerosis (5).