Genetic Modifiers in CF: Role of ABH polymorphisms

描述（由申请人提供）：病原体入侵宿主与宿主细胞表面的糖基化模式密切相关。糖基化模式受糖基转移酶的表达和活性调控；一些负责组织-血液（ABH）群系统的糖基转移酶也可能调节病原体结合的关键碳水化合物决定因素。因此，我们选择ABH分型作为一个关键的独立因素来验证糖基化模式的差异可能导致宿主-病原体相互作用的异常，从而导致囊性纤维化疾病的严重程度。一些表型特征，包括性别、营养状况和粪性肠梗阻（可能由回肠粘液异常糖基化引起）影响肺部严重程度，也将被评估。以下具体目标将被追求：(1)确定ABH通路基因多态性（包括ABO、FUT2[分泌状态]和FUT3 [Lewis抗原]）是否与“严重”或“轻度”肺部疾病或CF病原体定植分离；(2)确定ABH通路多态性与胎粪肠梗阻等非肺表型特征之间的关系。

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.