Program Schedule

768
Host Gene Polymorphisms and Susceptibility to Viral Enteropathogens in Children Living in The Gambia and Kenya

Session: Poster Abstract Session: Clinical Respiratory Infections
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: The Global Enteric Multicenter Study (GEMS) is a prospective case control study to determine pathogen specific diarrheal disease burden among children <5 years of age in Africa and Asia. Using samples from children in The Gambia and Kenya, we conducted a gene candidate study that examined the association of the host DNA single nucleotide polymorphisms (SNPs) and specific viral enteropathogens rotavirus and norovirus causing diarrhea.

Methods: Stool specimens from moderate to severe diarrhea cases and their age, sex and area matched controls were examined for the presence of enteropathogens and host DNA SNPs (N=144) in 26 genes that code for host proteins involved in pathogen attachment, inflammation, innate and acquired immune responses to enteropathogens. We analyzed the distribution of SNPs and compared cases vs. controls according to enteropathogens identified. Comparisons were made using SNPSTATs software following the dominant model. Logistic regression model was used to adjust for potential confounders including site and age.

Results: Microbiological and genotype data were available in 1,164 subjects. In The Gambia, diarrhea due to norovirus was associated with SNP in C3orf23 (69% vs. 36%, OR=4.0, CI=1.1.5-13.7, P=0.03), SNPs in IL12B (67% vs. 32%, OR=4.2, CI=1.19-15, P=0.025) and a SNP in MBL (29% vs. 58%, OR=0.3, CI=0.08-0.9, P=0.045) and diarrhea from rotavirus was associated with SNPs in CD180 (88% vs. 49%, OR=8, CI=1.66-35, P=0.003). In Kenya, diarrhea from norovirus was associated with a SNP in C3orf23 (71% vs. 23%, OR=8, CI=1.4-42, P=0.013), and SNPs in LPLUNC (50% vs.15%, OR=6, CI=1.5-21, P=0.012) and diarrhea from rotavirus was associated with LPLUNC (61% vs. 40%, OR=2.5, CI=1.2-5.3, P=0.011).

Conclusion: Distinct SNPs were associated with pathogen specific viral diarrhea in children under 5 years of age living in two African countries.

Roshni Daver, MBBS, MD1, Jitesh Shewale, DDS2, Brianna Lindsay, PhD3, Joseph Oundo, PhD4, Martin Antonio, PhD5, Sandra Panchalingam, PhD3, Debasish Saha, PhD6, Robert F. Breiman, MD7, Kelly Volcik, PhD1, Megan L. Grove, MS8, O. Colin Stine, PhD3, James Kaper, PhD3, Myron Levine, MD, FIDSA3, Karen Kotloff, MD3, James Nataro, MD, PhD9 and Pablo Okhuysen, MD10, (1)University of Texas, Medical School at Houston, Houston, TX, (2)University of Texas, School of Public Helath, Houston, TX, (3)University of Maryland, School of Medicine, Baltimore, MD, (4)Ministry of Public Health and Sanitation Kenya, Nairobi, Kenya, (5)The Medical Research Council Unit, Banjul, Gambia, (6)University of Otago, Dunedin, New Zealand, (7)Rollins School of Public Health, Emory University, Emory Global Health Institute, Atlanta, GA, (8)Human Genetics Center, University of Texas, School of Public Health, Houston, TX, (9)The University of Virginia, School of Medicine, Charlottesville, VA, (10)The University of Texas MD Anderson Cancer Center, Houston, TX

Disclosures:

R. Daver, None

J. Shewale, None

B. Lindsay, None

J. Oundo, None

M. Antonio, None

S. Panchalingam, None

D. Saha, None

R. F. Breiman, None

K. Volcik, None

M. L. Grove, None

O. C. Stine, None

J. Kaper, None

M. Levine, None

K. Kotloff, None

J. Nataro, None

P. Okhuysen, None

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