Genetic Variation Predicting Lactose Intolerance ( LCT -13910C>T), Dairy Intake, 25-Hydroxyvitamin D and Risk of Cardiometabolic Diseas

Background: The LCT-13910C>T variant is associated with lactose intolerance (LI) in >70 ethnic populations. In Canada, the prevalence of the LCT -13910C>T variant is not known. Individuals with LI might avoid dairy, which is a rich source of calcium and vitamin D. Dairy has been associated with increased risk of cardiometabolic diseases, but findings have been equivocal.;Objectives: To determine the prevalence of LI risk genotypes in major ethnic groups living in Canada and their association with 25(OH)D levels and biomarkers of cardiometabolic disease, and to determine food predictors of calcium and vitamin D in different LCT genotypes.;Methods: A total of 1,495 participants from the Toronto Nutrigenomics and Health (TNH) study were used for the present study. Fasting blood samples were obtained for genotyping, 25(OH)D, biomarkers of cardiometabolic disease, and plasma proteomics. Dairy intake was assessed using a 196-item semi-quantitative food frequency questionnaire.;Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other ethnicities had the CC genotype associated with LI. In Caucasians, compared to the TT genotype, those with the CC genotype had lower dairy intake, and plasma 25(OH)D levels. The CT and CC genotypes were associated with lower calcium intake and increased risk of suboptimal (<75 nmol/L) plasma 25(OH)D. Skim milk was the biggest predictor of calcium and vitamin D intake in those with the TT genotype, but not the CC genotype. Alpha chain fibrinogen levels were significantly lower in the CC genotype compared to the TT genotype. Levels of several plasma proteins were associated with dairy, cheese and milk intake only in those with the CC genotype (p.;<0.05).;Conclusions: In Caucasians, the CC genotype that predicts LI is associated with lower plasma 25(OH)D and higher levels of alpha chain fibrinogen which is due, at least in part, to lower dairy intake. Individuals with the CT genotype appear to have an intermediate phenotype. The association between dairy and the plasma proteome in those with the CC genotype suggests a potential involvement of the microbiome in mediating some of the physiological effects of lactose.