Study of the FUT2 gene association with infection and clinical manifestations of Helicobacter pylori infection

The aim of the pilot study of a group of adolescents with H. pylori infection was to study the preliminary data obtained on the rs602662 locus of the FUT2 gene and to establish its role in the realization of clinical manifestations of chronic gastritis, gastric ulcer and duodenal ulcer associated with H. pylori.Methods: The study included 91 patients. The study for the presence of the polymorphic locus rs602662 of the FUT2 gene was carried out by the standard TaqMan PCR method on a Real-Time CFX96 Touch amplifier. The duration of the study was 6 months.Results: The main group included 25 adolescents aged 16 to 17 years 11 months, the control group included 20 patients. Patients infected with H. pylori more often noticed symptoms of dyspepsia - in 36%, compared with the control group - 9.7%. The presence of a family history in the main group for associated diseases had a significant difference, χ2 = 4.97, p <0.05.To assess the contribution of the genotype of the rs602662 locus of the FUT2 gene to the risk of clinical manifestations in H. pylori infection, the main group was divided into subgroups. In the distribution of alleles in these groups, statistically significant differences were revealed.Allele “A” has a protective effect against the onset of clinical symptoms of dyspepsia. The odds ratio (OR) with the carriage of allele “A” (genotypes A / A and G / A versus G / G) to have clinical symptoms with a positive H. pylori status was 0.175 (CI = [0.049-0.625] chi2 = 7.79 p = 0.0053).Conclusion. As a result of the study, we were unable to identify a significant association of alleles and genotypes of the rs602662 locus of the FUT2 gene with clinical manifestations of H. pylori infection. At the same time, carriers of the A allele have a pronounced association with the absence of clinical symptoms in patients with a positive H. pylori infection status of 0.175 (C.I. = [0.049-0.625] chi2 = 7.79 p = 0.0053).

Comparative analysis of codon usage patterns of FUT2 from different species

Enterotoxigenic E. coli is an important zoonotic pathogen causing diarrhea in human and newborn animals. α - (1,2) fucosyltransferase 2 (FUT2) is closely associated with the formation of pathogenic receptors of Enterotoxigenic E. coli. Codon usage bias analysis can help to better understand the molecular mechanisms and evolutionary relationships of a particular gene. In order to understand the codon usage pattern of FUT2 gene, FUT2 gene coding sequences of nine species were selected from GenBank database for calculating the nucleotide composition (GC content) and genetic indices including effective number of codons, relative synonymous codon usage and relative codon usage bias using R software, in order to analyze codon usage bias and base composition in FUT2 gene from different species. The results showed that the codon usage of FUT2 gene in different species was affected by GC bias, especially GC frequency at the third position of codon (GC3). Most of the optimal codons were biased towards the G/C-ending types. GCC, CUG, UCC, GUG and AUC showed the highest relative synonymous codon usage value among different species, belonging to the most dominant codons. The usage characteristic of the codens for FUT2 gene in Sus scrofa was similar to that of Bos taurus; Homo sapiens was similar to Pan troglodytes. Effective number of codons was significantly, negatively correlated with GC3, and the relative higher frequency of optimal codon implied that FUT2 genes from different species had a strong bias in codon usage.

EXAMINING AN ASSOCIATION BETWEEN FUT2 GENE AND HELICOBACTER PYLORI INFECTION RELATED TO CLINICAL MANIFESTATIONS

The aim of the study was to examine an association of the rs602662 FUT2 genetic locus with the status of H. pylori infection and development of related diseases (chronic gastritis, gastric ulcer and 12 duodenal ulcer).Methods: The study included 91 patients, divided into two groups - "case" and "control". Criteria for the “case” group enrollment: diagnosis of gastric or duodenal ulcer, chronic non-atrophic gastritis; positive test for H. pylori.The “control” group included patients with episodic complaints of dyspepsia while undergoing a comprehensive examination, with negative test for H. pylori, as well as having no history of former therapy on H. pylori elimination.The study for the presence of the polymorphic locus rs602662 of the FUT2 gene was carried out by the standard TaqMan PCR method on a Real-Time CFX96 Touch amplifier. The follow-up period was 6 months.Results: The main group included 50 patients aged 21 to 50 years, the control group – 41 patients. Patients infected with H. pylori more often noticed symptoms of dyspepsia - in 36%, compared with the control group - 9.7%. A family history of associated diseases in the main group was significantly differed, χ2 = 4.97, p <0.05.To assess the contribution of the rs602662 locus genotype in FUT2 gene to the risk of clinically manifested H. pylori infection, the main group was divided into subgroups. In the distribution of alleles in these groups, significant differences were revealed. Allele "A" has a protective effect regarding the onset of clinical symptoms of dyspepsia. The odds ratio (OR) with the carriage of allele "A" (genotypes A / A and G / A versus G / G) to have clinical symptoms with a positive H. pylori status was 0.175 (CI = [0.049-0.625] chi2 = 7.79 p = 0.0053 ).Conclusion:1. No association of alleles and genotypes of the rs602662 locus of the FUT2 gene with the status of H. pylori infection was revealed.2. Carriage of allele "A" have a significant association with the absence of clinical symptoms in patients with a positive status of H. pylori infection, OR 0.175 (CI = [0.049-0.625] chi2 = 7.79 p = 0.0053).

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

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

Can the FUT 2 Gene Variant Have an Effect on the Body Weight of Patients Undergoing Bariatric Surgery?—Preliminary, Exploratory Study

Background: The FUT2 gene (Se gene) encoding the enzyme α-1,2-L-fucosyltransferase 2 seems to have a significant effect on the number and type of bacteria colonizing the intestines. Methods: In a group of 19 patients after bariatric surgery, the polymorphism (rs601338) of FUT2 gene was analyzed in combination with body mass reduction, intestinal microbiome (16S RNA sequencing), and short chain fatty acids (SCFA) measurements in stools. Results: Among the secretors (Se/Se polymorphism of the FUT2 gene rs601338, carriers of GG variant), correlations between waist-hip ratio (WHR) and propionate content and an increase in Prevotella, Escherichia, Shigella, and Bacteroides were observed. On the other hand—in non-secretors (carriers of GA and AA variants)—higher abundance of Enterobacteriaceae, Ruminococcaceae, Enterobacteriaceae, Clostridiales was recorded. Conclusions: The increased concentrations of propionate observed among the GG variants of FUT 2 may be used as an additional source of energy for the patient and may have a higher risk of increasing the WHR than carriers of the other variants (GA and AA).