Ileal Lactase Expression Associates with Lactase Persistence Genotypes.

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase () genotypes and intestinal expression of . We aimed to investigate ileal expression of depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m, of whom 17.4% were smoking. Ileal expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower expression (vs. AG = 2.2 × 10, vs. AA = 1.1 × 10). Homozygous major allele of rs3754689 (GG) was related to higher expression (vs. AG = 1.7 × 10, vs. AA = 0.0074). Rs3754689 genotype did not modify expression (GG vs. AG = 0.051) in rs4988235-heterozygous subgroup. Interestingly, , which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of expression (r = -0.57, p = 1.1 × 10); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between and expression in the ileum is striking and requires further investigation.