FUT2 Secretor Genotype and Susceptibility to Infections and Chronic Conditions in the ALSPAC Cohort

Wellcome Open Res. 2018 Sep 25;3:65. doi: 10.12688/wellcomeopenres.14636.2. eCollection 2018.

Abstract

Background: The FUT2 (fucosyltransferase-2) gene determines blood group secretor status. Being homozygous for the inactive "non-secretor" rs601338(A) allele confers resistance to certain infections (e.g. Norovirus, Rotavirus) and susceptibility to others (e.g. Haemophilus influenza, Streptococcus pneumonia). Non-secretors also have an increased risk of type 1 diabetes and inflammatory bowel disease. We examined FUT2 genotype, infections and chronic conditions in a population-based cohort. Methods: We studied 7,582 pregnant women from the ALSPAC pregnancy cohort. Infections (measles, mumps, chicken pox, whooping cough, meningitis, herpes, gonorrhea and urinary infections) and chronic conditions (kidney disease, hypertension, diabetes, rheumatism, arthritis, psoriasis, hay fever, asthma, eczema and allergies) were self-reported. FUT2 secretor status was determined from the rs601338 genotype. ABO blood type was obtained from clinical records. Results: Overall, 1920 women (25.3%) were homozygous for the non-secretor allele (AA). Secretor status was associated with mumps, with 68% of non-secretors experiencing this infection, compared to 48% of secretors (RR, 1.40; 95% CI, 1.34-1.46). A weaker association was observed for measles infection (76% vs. 72%; RR, 1.05; 95% CI, 1.02-1.09). Non-secretors also experienced an increased risk of kidney disease (5.4% vs. 3.9%; RR, 1.39; 95% CI, 1.11-1.75). Independent of secretor status, AB blood type was a risk factor for mumps (RR 1.15; 95%CI, 1.03, 1.28 compared to type O). We found no evidence of interaction between secretor status and blood type. For some conditions, including asthma and arthritis, FUT2 heterozygosity (GA) appeared to confer an intermediate phenotype. There was no strong evidence of association between secretor status and other infections or chronic conditions, although statistical power was limited for rare outcomes. Conclusion: Our results identify an association between FUT2 secretor status and self-reported kidney disease, and confirm a recently reported association with susceptibility to mumps infection. The clinical implications of these associations warrant further investigation.

Keywords: ALSPAC; FUT2; chronic disease; infection; kidney disease; mumps; secretor status.

Grant support

This research was undertaken, in part, thanks to funding from the Canada Research Chairs program. The UK Medical Research Council and the Wellcome Trust (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website. GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. MBA holds the Canada Research Chair in Developmental Origins of Chronic Disease. N.J.T. is a Wellcome Trust Investigator (202802/Z/16/Z), works within the University of Bristol NIHR Biomedical Research Centre (BRC) (IS-BRC-1215) and as part of the Cancer Research UK Integrative Cancer Epidemiology Programme (C18281/A19169). K.H.W. is funded equally by two programs of the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/3 and MC_UU_12013/4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This publication is the work of the authors and M.B.A. will serve as guarantor for the contents of this paper.