Genetic Modifiers in CF: Role of ABH polymorphisms

描述（由申请方提供）：病原体侵入宿主与宿主细胞表面糖基化模式密切相关。糖基化模式由糖基转移酶的表达和活性调节;负责组织-血液（ABH）组系统的几种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簇。因此，我们选择ABH分型作为一个关键的独立因素来检验糖基化模式的差异可能导致宿主-病原体相互作用异常的假设，从而有助于囊性纤维化疾病的严重程度。包括性别、营养状态和胎粪性肠梗阻（可能由回肠粘液糖基化异常引起）在内的几种表型特征影响肺部严重程度，也将进行评价。将追求以下具体目标：（1）确定ABH通路（包括ABO、FUT 2 [分泌状态]和FUT 3 [刘易斯抗原]）中基因的多态性是否与“重度”或“轻度”肺病或CF病原体定植分离;（2）确定ABH通路中多态性与非肺表型特征（如胎粪性肠梗阻）之间的关联。

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.