Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25-Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study

Background: The LCT-13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake. Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH) D concentrations. Methods: Blood samples were drawn from a total of 1495 men and women aged 20-29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH) D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT-13910C>T genotypes was compared by using x(2) analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH) D concentrations. Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean +/- SE total dairy intake (2.15 +/- 0.09 compared with 2.67 +/- 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 +/- 0.03 compared with 0.46 +/- 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH) D concentration (63 +/- 1.9 compared with 75.8 +/- 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH) D concentration (< 75 nmol/L). Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH) D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype.