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Jovanka R King, Jezabel Varadé, Lennart Hammarström
Background: Single-nucleotide polymorphisms (SNPs) in the fucosyltransferase genes FUT2 and FUT3 have been associated with susceptibility to various infectious and inflammatory disorders. FUT variations influence the expression of human histo-blood group antigens (HBGAs) (H-type 1 and Lewis), which are highly expressed in the gut and play an important role in microbial attachment, metabolism, colonization, and shaping of the microbiome. In particular, FUT polymorphisms confer susceptibility to specific rotavirus and norovirus genotypes, which has important global health implications...
December 9, 2018: Journal of the Pediatric Infectious Diseases Society
Raul Cabrera-Rubio, Clemens Kunz, Silvia Rudloff, Izaskun Garcia-Mantrana, Elena Crehuá-Gaudiza, Cecilia Martinez-Costa, Maria C Collado
BACKGROUND AND OBJECTIVES: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. METHODS: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing...
December 11, 2018: Journal of Pediatric Gastroenterology and Nutrition
Regie Lyn P Santos-Cortez, Charlotte M Chiong, Daniel N Frank, Allen F Ryan, Arnaud P J Giese, Tori Bootpetch Roberts, Kathleen A Daly, Matthew J Steritz, Wasyl Szeremeta, Melquiadesa Pedro, Harold Pine, Talitha Karisse L Yarza, Melissa A Scholes, Erasmo Gonzalo D V Llanes, Saira Yousaf, Norman Friedman, Ma Leah C Tantoco, Todd M Wine, Patrick John Labra, Jeanne Benoit, Amanda G Ruiz, Rhodieleen Anne R de la Cruz, Christopher Greenlee, Ayesha Yousaf, Jonathan Cardwell, Rachelle Marie A Nonato, Dylan Ray, Kimberly Mae C Ong, Edward So, Charles E Robertson, Jordyn Dinwiddie, Sheryl Mae Lagrana-Villagracia, Samuel P Gubbels, Rehan S Shaikh, Stephen P Cass, Elisabet Einarsdottir, Nanette R Lee, David A Schwartz, Teresa Luisa I Gloria-Cruz, Michael J Bamshad, Ivana V Yang, Juha Kere, Generoso T Abes, Jeremy D Prager, Saima Riazuddin, Abner L Chan, Patricia J Yoon, Deborah A Nickerson, Eva Maria Cutiongco-de la Paz, Sven-Olrik Streubel, Maria Rina T Reyes-Quintos, Herman A Jenkins, Petri Mattila, Kenny H Chan, Karen L Mohlke, Suzanne M Leal, Lena Hafrén, Tasnee Chonmaitree, Michele M Sale, Zubair M Ahmed
Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗ ) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p...
November 1, 2018: American Journal of Human Genetics
Sheila J Barton, Robert Murray, Karen A Lillycrop, Hazel M Inskip, Nicholas C Harvey, Cyrus Cooper, Neerja Karnani, Irma Silva Zolezzi, Norbert Sprenger, Keith M Godfrey, Aristea Binia
Background: Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported gastrointestinal and respiratory illnesses in infancy. Methods: In the Southampton Women's Survey, FUT2 genetic variants (single-nucleotide polymorphisms [SNPs] rs601338 and rs602662) were genotyped in 1831 infants and related to infant illnesses, after adjustment for sex, breastfeeding duration, and potential confounders...
October 30, 2018: Journal of Infectious Diseases
Zhengchang Wu, Haiyue Feng, Yue Cao, Yanjie Huang, Chaohui Dai, Shenglong Wu, Wenbin Bao
Escherichia coli ( E. coli ) F18 is the main pathogen responsible for post-weaning diarrhea (PWD) in piglets. Resistance to E. coli F18 depends on the expression of the cognate receptors in the intestinal epithelial cells. However, the molecular mechanism of E. coli F18 resistance in weaned piglets remains unclear. Here, we performed a comparative transcriptome study of the duodenal tissue from Sutai E. coli F18 sensitive and resistant pigs by RNA-seq, and pig α(1,2) fucosyltransferase 2 ( FUT2 ) was identified as a host differentially expressed gene controlling the E...
October 24, 2018: International Journal of Molecular Sciences
Meghan B Azad, Kaitlin H Wade, Nicholas J Timpson
Background: The FUT2 (fucosyltransferase 2) gene encodes alpha (1,2) fucosyltransferase, which determines blood group secretor status. Being homozygous for the inactive "non-secretor" rs601338(A) allele appears to confer resistance to certain infections (e.g. Norovirus , Rotavirus and Helicobacter pylori ) and susceptibility to others (e.g. Haemophilus influenza and Streptococcus pneumonia ). Non-secretors also have an increased risk of type 1 diabetes and inflammatory bowel disease. We aimed to determine the association of the FUT2 secretor genotype with infections and chronic conditions in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC)...
2018: Wellcome Open Research
Helene Gellert-Kristensen, Nawar Dalila, Sune Fallgaard Nielsen, Børge Grønne Nordestgaard, Anne Tybjaerg-Hansen, Stefan Stender
Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify new genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic associations with gallstone disease from the Global Biobank Engine (GBE), an online browser of genomewide associations in UK Biobank participants (14,940 cases and 322,268 controls)...
October 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Khadija El Jellas, Bente B Johansson, Karianne Fjeld, Aristotelis Antonopoulos, Heike Immervoll, Man H Choi, Dag Hoem, Mark E Lowe, Dominique Lombardo, Pål R Njølstad, Anne Dell, Eric Mas, Stuart M Haslam, Anders Molven
Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C-terminus of CEL/FAPP...
October 12, 2018: Journal of Biological Chemistry
Edward P K Parker, Helena Whitfield, Chudarkodi Baskar, Sidhartha Giri, Jacob John, Nicholas C Grassly, Gagandeep Kang, Ira Praharaj
The FUT2 gene determines whether histo-blood group antigens are secreted at mucosal surfaces. Secretor status influences susceptibility to enteric viruses, potentially including oral poliovirus vaccine (OPV). We performed a nested case-control study to determine the association between FUT2 genotype (SNPs G428A, C302T, and A385T) and seroconversion among Indian infants who received a single dose of monovalent type 3 OPV. Secretor prevalence was 89/118 (75%) in infants who seroconverted and 97/122 (80%) in infants who failed to seroconvert (odds ratio 0...
September 19, 2018: Journal of Infectious Diseases
Katri Korpela, Anne Salonen, Brandon Hickman, Clemens Kunz, Norbert Sprenger, Kaarina Kukkonen, Erkki Savilahti, Mikael Kuitunen, Willem M de Vos
One of the most abundant components in human milk is formed by oligosaccharides, which are poorly digested by the infant. The oligosaccharide composition of breast milk varies between mothers, and is dependent on maternal secretor (FUT2) genotype. Secretor mothers produce milk containing α1-2 fucosylated human milk oligosaccharides, which are absent in the milk of non-secretor mothers. Several strains of bacteria in the infant gut have the capacity to utilise human milk oligosaccharides (HMOs). Here we investigate the differences in infant gut microbiota composition between secretor (N = 76) and non-secretor (N = 15) mothers, taking into account birth mode...
September 13, 2018: Scientific Reports
Wei Liang, Feng Cai, Liang Yang, Zhe Zhang, Zhicheng Wang
Background: The para-Bombay phenotype is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for seven Chinese individuals serologically typed as para-Bombay in Blood Station Center of Ningbo, Zhejiang Province, Ningbo, China from 2011 to 2014. Methods: RBCs' phenotype was characterized by standard serologic technique. Genomic DNA was sequenced with primers that amplified the coding sequence of α (1, 2)-fucosyltransferase genes FUT1 (or H ) and FUT2 (or Se ), respectively...
August 2018: Iranian Journal of Public Health
Yasuhiro Omata, Reiji Aoki, Ayako Aoki-Yoshida, Keiko Hiemori, Atsushi Toyoda, Hiroaki Tateno, Chise Suzuki, Yoshiharu Takayama
Psychological stress can cause dysfunction of the gastrointestinal tract by regulating its interaction with central nervous system (brain-gut axis). Chronic social defeat stress (CSDS) is widely used to produce a rodent model of stress-induced human mood disorders and depression. We previously showed that CSDS significantly affects the intestinal ecosystem including cecal and fecal microbiota, intestinal gene expression profiles and cecal metabolite profiles. Here, we investigated whether the glycosylation pattern in the intestinal epithelium was affected in C57BL/6 mice exposed to CSDS (hereinafter referred to as CSDS mice)...
September 4, 2018: Scientific Reports
Peter Arend
The metabolic relationship between the formation of the ABO(H) blood group phenotype and human fertility is evident in the case of the (Oh) or Bombay blood type, which Charles Darwin would have interpreted as resulting from reduced male fertility in consanguinities, based on the history of his own family, the Darwin/Wedgwood Dynasty. The classic Bombay type occurs with the extremely rare, human-specific genotype (h/h; se/se), which (due to point mutations) does not encode fucosyltransferases 1(FUT1) and 2 (FUT2)...
November 2018: Immunobiology
Lynda Mottram, Jining Liu, Sonali Chavan, Joshua Tobias, Ann-Mari Svennerholm, Jan Holgersson
We have previously reported clinical data to suggest that colonization factor I (CFA/I) fimbriae of enterotoxigenic Escherichia coli (ETEC) can bind to Lewis a (Lea ), a glycan epitope ubiquitous in the small intestinal mucosa of young children (<2 years of age), and individuals with a genetic mutation of FUT2. To further elucidate the physiological binding properties of this interaction, we engineered Chinese Hamster Ovary (CHO-K1) cells to express Lea or Leb determinants on both N- and O-glycans. We used our glyco-engineered CHO-K1 cell lines to demonstrate that CfaB, the major subunit of ETEC CFA/I fimbriae, as well as four related ETEC fimbriae, bind more to our CHO-K1 cell-line expressing Lea , compared to cells carrying Leb or the CHO-K1 wild-type glycan phenotype...
July 26, 2018: Scientific Reports
Guoqing Deng, Lvao Chen, Yuqi Zhang, Sairong Fan, Wencan Li, Jianxin Lu, Xiaoming Chen
Fucosyltransferase 2 (FUT2), the enzyme catalyzing α-1,2-fucosylation in mammals, has been implicated in cancer. The up-regulation of FUT2 has been observed in lung adenocarcinoma (LUAD), and FUT2 can enhance the cell migration and invasion of LUAD cell lines. However, the underlying mechanism of FUT2 in LUAD remains largely unknown. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during lung cancer metastasis and progression. In the present study, we showed that knocking down FUT2 in LUAD cell lines increased the expression of E-cadherin and reduced the expression of Vimentin, N-cadherin, TβRII, p-Smad2, p-Smad3 and Snail, which were the makers of EMT...
September 15, 2018: Experimental Cell Research
Gunn-Helen Moen, Elisabeth Qvigstad, Kåre I Birkeland, David M Evans, Christine Sommer
Background: Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality. Objectives: The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2)...
August 1, 2018: American Journal of Clinical Nutrition
Martin Palus, Yahya Sohrabi, Karl W Broman, Hynek Strnad, Matyáš Šíma, Daniel Růžek, Valeriya Volkova, Martina Slapničková, Jarmila Vojtíšková, Lucie Mrázková, Jiří Salát, Marie Lipoldová
BACKGROUND: Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, carrying 12...
July 6, 2018: BMC Neuroscience
Lucy Thorne, Angela Nalwoga, Alexander J Mentzer, Alexis de Rougemont, Myra Hosmillo, Emily Webb, Margaret Nampiija, Allan Muhwezi, Tommy Carstensen, Deepti Gurdasani, Adrian V Hill, Manj S Sandhu, Alison Elliott, Ian Goodfellow
Background: Human noroviruses (HuNoVs) are a prominent cause of gastroenteritis, yet fundamental questions remain regarding epidemiology, diversity, and immunity in sub-Saharan African children. We investigated HuNoV seroprevalence and genetic and sociodemographic risk factors in Ugandan children. Methods: We randomly screened 797 participants of a longitudinal birth cohort (Entebbe, EMaBS) and 378 from a cross-sectional survey (rural Lake Victoria, LaVIISWA), for antibodies against HuNoV genotypes by ELISA...
July 24, 2018: Journal of Infectious Diseases
Jialei Hu, Zi Wang, Yujia Shan, Yue Pan, Jia Ma, Li Jia
Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis...
June 15, 2018: Cell Death & Disease
Haifei Wang, Sen Wu, Jiayun Wu, Shouyong Sun, Shenglong Wu, Wenbin Bao
The FUT2 gene was considered as an important candidate for pathogenic infections, while the potential associations between this gene and the production and reproductive traits of pigs have not been explored. In this study, we detected the genetic variants of porcine FUT2 gene and analyzed the associations of the polymorphisms with FUT2 mRNA expression and production and reproductive traits (age at 100 kg, backfat thickness at 100 kg, eye muscle thickness, the number of newborn piglets, the number of weaned piglets, and birth weight) in 100 Large White sows...
February 2018: Genes & Genomics
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