A Study Identifies a Gene Variant that Reduces the Susceptibility to Diarrhoea Among Small Children

The results provide further evidence that host genetic factors can in part explain susceptibility to diarrhoeal disease

Photo: Christine Cabalo

An international study led by Dr. Jordi Sunyer, Head of the Child Health Programme at ISGlobal, identifies a variant of the FUT2 gene that is linked to a lower risk of diarrhoea. The results, obtained through a of genome wide association meta-analysis of diarrhoeal disease in small children in developing countries, were published in the journal Human Molecular Genetics.

Diarrhoeal disease, although preventable and treatable, is the second leading cause of death in children under five years old, and is responsible for killing around 760 000 children every year. While in developing countries it is caused by different types of pathogens (virus, bacteria and parasites), in developed most diarrhoeas are caused by viral infections (namely, Rotavirus, Norovirus and Adenovirus). There is growing evidence that host genetic factors can explain part of the differences in susceptibility and response to infection between individuals.

The aims of the study were to identify genetic variants that confer susceptibility to diarrhoeal disease in young children from developed countries and to elucidate the potential biological mechanisms involved. To do so, the authors performed a genome-wide association meta-analysis (combining the results from multiple studies) in the context of a large consortium of birth cohorts with  more than 5,000 children (EAGLE, for Early Genetics and Lifecourse Epidemiology).

The analysis identified and replicated a significant association with a variant of the FUT2 gene: children with the genetic variant (or allele) which results in a truncated protein had lower risk of diarrhoea. The FUT2 protein participates in the production of histo-blood antigens. Children with a truncated protein cannot produce certain antigens which are used by certain virus such as Rotavirus and Norovirus to enter the cell. Other potential biological mechanisms identified were the regulation of ion transport and blood pressure. "The organs implicated in the disease were, as expected, the gastrointestinal tract and the immune system, but we also identified the neurosecretory system" points out Mariona Bustamante, first author of the study.

This FUT2 genetic variant had previously been linked to lower infection by Rotavirus and Norovirus in studies of hospitalized subjects, and is associated to higher risk of inflammatory bowel disease. However, as senior author Jordi Sunyer points out, “we cannot exclude the possibility that the results reflect different levels of exposure to the virus, rather than a higher susceptibility to infection”. The authors conclude that future studies with larger sample sizes and more specific diagnoses will allow the identification of other genetic variants related to diarrheal disease .  


Bustamante M, Standl M, Bassat Q, Vilor-Tejedor N, Medina-Gomez C, et al. A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. Hum Mol Genet. 2016 Aug 23.