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The <jats:italic>CFTR<\/jats:italic> genotype is invariably correlated with pancreatic status\u2014in about 85% of cases with pancreatic insufficiency and in about 15% of cases with pancreatic sufficiency. The correlations between the <jats:italic>CFTR<\/jats:italic> genotype and pulmonary, liver, and gastrointestinal expression are debatable. The heterogeneous phenotype in CF patients bearing the same genotype or homozygotes for nonsense mutations implicated environmental and\/or genetic factors in the disease. However, the discordant phenotype observed in CF siblings argued against a major role of environmental factors and suggested that genes other than <jats:italic>CFTR<\/jats:italic> modulate the CF phenotype. A locus that modulates gastrointestinal expression was identified in mice and subsequently in humans. By analyzing nine CF patients discordant for meconium ileus we were able to show that this locus had a dominant effect. Moreover, in a collaborative study we found a higher rate of polymorphisms in \u03b2\u2010defensin genes 1 and 2 in CF patients and in controls. In another multicenter study mutations in \u03b1\u20101 antitrypsin (<jats:italic>A1AT<\/jats:italic>) and mannose binding lectin genes were found to be independent risk factors for liver disease in CF patients. The body of evidence available suggests that the variegated CF phenotype results from complex interactions between numerous gene products. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.10461","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T11:52:48Z","timestamp":1033905168000},"page":"88-95","source":"Crossref","is-referenced-by-count":131,"title":["Genotype\u2013phenotype correlation in cystic fibrosis: The role of modifier 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