FUT2 Genetic Variants and Reported Respiratory and Gastrointestinal Illnesses During Infancy

被引:25
作者
Barton, Sheila J. [1 ]
Murray, Robert [2 ]
Lillycrop, Karen A. [2 ,5 ]
Inskip, Hazel M. [1 ,3 ,4 ]
Harvey, Nicholas C. [1 ,3 ,4 ]
Cooper, Cyrus [1 ,3 ,4 ]
Karnani, Neerja [6 ,7 ]
Zolezzi, Irma Silva [8 ]
Sprenger, Norbert [8 ]
Godfrey, Keith M. [1 ,2 ,3 ,4 ]
Binia, Aristea [8 ]
机构
[1] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England
[2] Univ Southampton, Human Dev & Hlth Acad Unit, Southampton, Hants, England
[3] Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England
[4] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
[5] Univ Southampton, Southampton Gen Hosp, Sch Biol Sci, Southampton, Hants, England
[6] ASTAR, Singapore Inst Clin Sci, Singapore, Singapore
[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore
[8] Nestle SA, Nestle Res Ctr, Lausanne, Switzerland
基金
英国医学研究理事会; 英国工程与自然科学研究理事会;
关键词
FUT2; variants; gastrointestinal and respiratory illnesses; pediatric illnesses; SECRETOR STATUS; MICROBIOTA COMPOSITION; YOUNG-CHILDREN; ROTAVIRUS; ASSOCIATION; INFECTIONS; DISEASE; SUSCEPTIBILITY; RESISTANCE; GASTROENTERITIS;
D O I
10.1093/infdis/jiy582
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. Results For FUT2 SNP rs601338, the risk ratios for 1 bout of diarrhea during ages 6-12 months and ages 12-24 months per additional risk (G) allele were 1.23 (95% confidence interval [CI], 1.08-1.4; P = .002) and 1.41 (95% CI, 1.24-1.61; P = 1.7 x 10(-7)), respectively; the risk ratio for 1 diagnosis of a lower respiratory illness (ie, pneumonia or bronchiolitis) during ages 12-24 months per additional G allele was 2.66 (95% CI, 1.64-4.3; P = .00007). Similar associations were found between rs602662 and gastrointestinal and respiratory illnesses, owing to the high linkage disequilibrium with rs601338 (R-2 = 0.92). Longer breastfeeding duration predicted a lower risk of diarrhea, independent of infant FUT2 genotype. Conclusions We confirmed that FUT2 G alleles are associated with a higher risk of infant gastrointestinal illnesses and identified novel associations with respiratory illnesses. FUT2 locus variants need consideration in future studies of gastrointestinal and respiratory illnesses among infants. The study confirms the role of fucosyltransferase 2 in the risk of reported gastrointestinal illnesses in a United Kingdom population and reports novel associations with respiratory illnesses and comorbidities. Breastfeeding has a protective role against the risk of illnesses, independent of FUT2 variants.
引用
收藏
页码:836 / 843
页数:8
相关论文
共 33 条
[1]  
[Anonymous], 2012, BMC PUBLIC HLTH, DOI DOI 10.1186/1471-2458-12-220
[2]  
[Anonymous], 2016, REPROD MATERNAL NEWB
[3]   A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways [J].
Bustamante, Mariona ;
Standl, Marie ;
Bassat, Quique ;
Vilor-Tejedor, Natalia ;
Medina-Gomez, Carolina ;
Bonilla, Carolina ;
Ahluwalia, Tarunveer S. ;
Bacelis, Jonas ;
Bradfield, Jonathan P. ;
Tiesler, Carla M. T. ;
Rivadeneira, Fernando ;
Ring, Susan ;
Vissing, Nadja H. ;
Fink, Nadia R. ;
Jugessur, Astanand ;
Mentch, Frank D. ;
Ballester, Ferran ;
Kriebel, Jennifer ;
Kiefte-de Jong, Jessica C. ;
Wolsk, Helene M. ;
Llop, Sabrina ;
Thiering, Elisabeth ;
Beth, Systke A. ;
Timpson, Nicholas J. ;
Andersen, Josefine ;
Schulz, Holger ;
Jaddoe, Vincent W. V. ;
Evans, David M. ;
Waage, Johannes ;
Hakonarson, Hakon ;
Grant, Struan F. A. ;
Jacobsson, Bo ;
Bonnelykke, Klaus ;
Bisgaard, Hans ;
Smith, George Davey ;
Moll, Henriette A. ;
Heinrich, Joachim ;
Estivill, Xavier ;
Sunyer, Jordi .
HUMAN MOLECULAR GENETICS, 2016, 25 (18) :4127-4142
[4]   ABO antigen and secretor statuses are not associated with gut microbiota composition in 1,500 twins [J].
Davenport, Emily R. ;
Goodrich, Julia K. ;
Bell, Jordana T. ;
Spector, Tim D. ;
Ley, Ruth E. ;
Clark, Andrew G. .
BMC GENOMICS, 2016, 17
[5]   Prolonged and Exclusive Breastfeeding Reduces the Risk of Infectious Diseases in Infancy [J].
Duijts, Liesbeth ;
Jaddoe, Vincent W. V. ;
Hofman, Albert ;
Moll, Henriette A. .
PEDIATRICS, 2010, 126 (01) :E18-E25
[6]   A Natural History of FUT2 Polymorphism in Humans [J].
Ferrer-Admetlla, Anna ;
Sikora, Martin ;
Laayouni, Hafid ;
Esteve, Anna ;
Roubinet, Francis ;
Blancher, Antoine ;
Calafell, Francesc ;
Bertranpetit, Jaume ;
Casals, Ferran .
MOLECULAR BIOLOGY AND EVOLUTION, 2009, 26 (09) :1993-2003
[7]   Cell attachment protein VP8*of a human rotavirus specifically interacts with A-type histo-blood group antigen [J].
Hu, Liya ;
Crawford, Sue E. ;
Czako, Rita ;
Cortes-Penfield, Nicolas W. ;
Smith, David F. ;
Le Pendu, Jacques ;
Estes, Mary K. ;
Prasad, B. V. Venkataram .
NATURE, 2012, 485 (7397) :256-U147
[8]   A FUT2 Gene Common Polymorphism Determines Resistance to Rotavirus A of the P[8] Genotype [J].
Imbert-Marcille, Berthe-Marie ;
Barbe, Laure ;
Dupe, Mathilde ;
Le Moullac-Vaidye, Beatrice ;
Besse, Bernard ;
Peltier, Cecile ;
Ruvoen-Clouet, Nathalie ;
Le Pendu, Jacques .
JOURNAL OF INFECTIOUS DISEASES, 2014, 209 (08) :1227-1230
[9]   Cohort profile: The Southampton Women's Survey [J].
Inskip, HM ;
Godfrey, KM ;
Robinson, SM ;
Law, CM ;
Barker, DJP ;
Cooper, C .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2006, 35 (01) :42-48
[10]   Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis [J].
Kambhampati, Anita ;
Payne, Daniel C. ;
Costantini, Veronica ;
Lopman, Benjamin A. .
CLINICAL INFECTIOUS DISEASES, 2016, 62 (01) :11-18