FUT Genotypes, Secretor Status, H.pylori Antibody Levels and Vitamin-B12 Concentrations in Indians

Abstract Objectives Background: The FUT2 gene is responsible for the secretion of ABO blood type antigens into the body fluids (saliva, mucous, urine, tears, breast milk, sweat, and semen). Those who secrete the antigens into body fluids are call secretors, those who do not are called non-secretors. Hypothesis: GWAS studies have reported FUT gene variants to be associated with circulating vitamin-B12 (Vit-B12) concentrations. Missense mutations in the FUT2 gene result in a non-secretor phenotype. Thus, the secretory status of an individual may affect circulating vitamin-B12 concentrations over and above the genotype. Methods Materials and Methods: We included 780 participants (271 children, 282 mothers, and 227 fathers) from Pune Maternal Nutrition Study (PMNS). We measured the secretor status of individuals in saliva by hemagglutination test. A total of eight genetic variants including six SNPs from the FUT2 gene (rs492602, rs681343, rs281377, rs601338, rs1800027, and rs602662) and two SNPs from the FUT6 gene (rs3760776 and rs3760775) from our previous GWAS study were correlated with circulating vitamin-B12 levels. We tested the associations of FUT gene variants with secretor status phenotype and of the secretor phenotype with circulating vit-B12, folate, and ferritin concentrations in addition to H.pylori antibody levels. Results Results and Discussion: We found 33% of participants were non-secretors compared to 20% reported in Western Caucasian populations. Non-secretors had higher vitamin-B12 concentrations but not of folate and ferritin, vitamin-B12 associations were over and above FUT genotypes. Non-secretors showed a higher response to Vit-B12 supplementation. We found a FUT2 haplotype () to be strongly associated with Vit-B12 concentrations and non-secretor status. Non-secretors had lower H.pylori antibody concentrations. FUT6 genotype and haplotype were associated with Vit-B12 concentrations but not with secretor status and H.pylori antibody levels. Conclusions Our data suggest that secretor status may influence Vit-B12 concentrations through susceptibility to H.pylori infection and possibly other gut microbiota. A higher frequency of non-secretors in Indians could offer a selective advantage against Vit-B12 deficiency. Funding Sources BBSRC, UK; MRC, UK; WELLCOME TRUST, UK; DBT, India; ICMR India