Genetic Modifiers in CF: Role of ABH polymorphisms

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DESCRIPTION (provided by applicant): Pathogen invasion of the host is intimately linked to patterns of glycosylation on host cell surfaces. Glycosylation patterns are regulated by the expression and activity of glycosyltransferases; several glycosyltransferases responsible for the histo-blood (ABH) group system may also regulate key carbohydrate determinants of pathogen binding. Therefore, we have chosen ABH typing as a key independent factor to test the hypothesis that differences in glycosylation patterns may lead to abnormalities in host-pathogen interactions, and thus, contribute to the severity of disease in cystic fibrosis. Several phenotypic characteristics including gender, nutritional status, and meconium ileus (which may result from abnormal glycosyation of ileal mucus) affect pulmonary severity and will also be evaluated. The following specific aims will be pursued: (1) Determine whether polymorphisms in genes in the ABH pathway (including ABO, FUT2 [Secretor status], and FUT3 [Lewis antigen]) segregate with "severe" or "mild" lung disease, or with CF pathogen colonization; (2) Determine the association between polymorphisms in the ABH pathway and nonpulmonary phenotype characteristics, such as meconium ileus.