FUT2 secretor genotype and susceptibility to infections and chronic conditions in the ALSPAC cohort.

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). Methods: This study included 7,582 pregnant women from the ALSPAC pregnancy cohort. Personal history of infections (measles, mumps, chicken pox, whooping cough, cold sores, meningitis, genital herpes, gonorrhea and urinary infections) and chronic conditions (kidney disease, hypertension, diabetes, rheumatism, arthritis, psoriasis, hay fever, asthma, eczema and various allergies) were self-reported by standardized questionnaire. FUT2 secretor status was determined from the rs601338 genotype. Results: Overall, 1920 women (25.3%) were homozygous for the FUT2 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; p<0.0001). A weaker association was observed for measles infection (76% vs. 72%; RR, 1.05; 95% CI, 1.02-1.09; p=0.0008). Non-secretors also experienced a 39% increased risk of kidney disease (5.4% vs. 3.9%; RR, 1.39; 95% CI, 1.11-1.75; p=0.004). For some conditions, including gonorrhea and arthritis, FUT2 heterozygosity (GA) appeared to confer an intermediate phenotype. There was no strong evidence of association between FUT2 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 kidney disease, and confirm a recently reported association with susceptibility to mumps infection. The clinical implications of these associations warrant further investigation.