Ileal Lactase Expression Associates with Lactase Persistence Genotypes.

Area of Science:

• Genetics
• Gastroenterology
• Molecular Biology

Background:

• Lactose digestion relies on lactase persistence genotypes, with varying global frequencies.
• The relationship between lactase (LCT) gene genotypes and intestinal LCT expression is not well understood.
• Investigating genetic polymorphisms' impact on LCT expression is crucial for understanding lactose digestion.

Purpose of the Study:

• To examine how LCT gene expression in the ileum is influenced by genetic polymorphisms (rs4988235, rs3754689, rs3739022).
• To determine the effect of age, sex, smoking status, and body mass index (BMI) on ileal LCT expression.
• To explore correlations between LCT expression and other gene expressions in the ileum.

Main Methods:

• Utilized phenotype, array-based genotype, and ileal mucosal biopsy expression data from the CEDAR study.
• Analyzed data from 196 healthy European participants.
• Performed statistical analyses to assess the association between genotypes, demographic factors, and LCT expression.

Main Results:

• Ileal LCT expression was largely independent of age, sex, BMI, and smoking status.
• The rs4988235 GG genotype was associated with significantly lower LCT expression.
• The rs3754689 GG genotype was linked to higher LCT expression, though this effect was not significant in rs4988235-heterozygous individuals.
• CD14, a marker for monocytes and macrophages, showed the strongest negative correlation with LCT expression (r = -0.57, pFDR = 1.1 × 10^-14).

Conclusions:

• Both rs4988235 and rs3754689 genetic polymorphisms are associated with ileal LCT expression.
• Factors like age, sex, smoking, and BMI do not significantly impact ileal LCT expression.
• The strong inverse correlation between LCT and CD14 expression in the ileum warrants further investigation.