ENVIRONMENTAL (LACK OF BREASTFEEDING) AND GENETIC (NOD2/CARD15) RISK FACTORS IN PEDIATRIC ONSET CROHN'S DISEASE (CD)

Abstract

Background: The etiology of CD is thought to involve a combination of genetic and environmental factors. The only established environmental risk factor for CD is smoking. Studies of other environmental factors such as infections, microbials, and breastfeeding have been inconclusive. This matched case-control study was designed to evaluate whether breastfeeding in the presence or absence of CARD15 is a risk for development of CD in children. Methods: Cases were recruited from the IBD Clinic at Children's Hospital of Wisconsin. Controls were recruited from the unaffected siblings of the cases and matched to unrelated cases by age and gender. Data was obtained by questionnaire from all subjects and/or their parents. DNA was genotyped for CARD15 in cases and controls by Taqman. Data for 53 pairs of subjects were compared by McNemar's test and Student's paired t-test. Matched odds ratios (OR) and confidence intervals (CI) were calculated. Results: Lack of breastfeeding in infancy tended towards significance as a risk factor for CD in children [OR = 2.33 (95% CI 0.84-7.41) P = 0.12]. However, the duration of breastfeeding was significantly shorter in children who developed CD than in unaffected siblings matched by age and gender [mean 3.25 SD 4.41 months vs. mean 5.77 SD 6.98 months, P = 0.05]. Genotype frequency of CARD15 in CD cases was 38% while in controls it was 21%. Conclusions: These preliminary findings suggest lack of breastfeeding in infancy may be a risk factor for the development of CD in children but is currently underpowered. Additional 90 CD cases have been recruited (controls are still being recruited)to adequately power this study. Completion of this data set with interaction analysis between CARD15 and breastfeeding will be available in near future. We speculate that clarifying the interactions between breastfeeding and genotype (CARD15) based on this study will lead to a clearer understanding of these gene-environmental interactions and provide insight for improved prevention and treatment.