Genetic Modifiers of Liver Disease in Cystic Fibrosis

Abstract

for the Gene Modifier Study Group C YSTIC FIBROSIS (CF) IS A REcessive monogenic disorder characterizedbymultiorganinvolvement and clinical heterogeneity that is incompletely explained by mutations within the cystic fibrosis transmembraneconductanceregulator(CFTR) gene (OMIM 602421). 1 Patients with CF, including those homozygous for DF508, smallfraction(Ϸ3%-5%)ofpatientswith CF develops severe liver disease characterized by cirrhosis with portal hypertension (CFLD) 1 ; thus, non-CFTR genetic variability may contribute to risk for severe liver disease. [14][15][16][17] To determine the association between non-CFTR genetic polymorphisms and CFLD, we studied 9 functional variants in 5 genes previously See also Patient Page.

Extensive Molecular Analysis Suggested the Strong Genetic Heterogeneity of Idiopathic Chronic Pancreatitis

“…All cases presented an early onset (17)(18)(19), that is, they were diagnosed within the first three decades of life. Exclusion criteria (MBL2, SCNN1G, SERPINA1, TGFB1 and TNFRSF1A) (31,32) Furthermore, we established a minimum threshold in Qscore of 30 (base call accuracy of 99.9%). All identified variants were analyzed with bioinformatics software that evaluates the impact of the change in amino-acidic structure on protein functionality with several parameters, and we filtered all variants to retain those alterations with high disease-causing potential.…”

Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease: Figure 1:

“…26 Although the homozygous ZZ genotype is necessary for liver disease to develop, a heterozygous Z mutation may act as a genetic modifier for other diseases by conferring a greater risk of more severe liver disease, such as in hepatitis C infection and cystic fibrosis liver disease. 27,28 Who should be screened?…”

The Prognosis of Cystic Fibrosis - A Clinician's Perspective

“…Variation in TCF7L2 (10q) was reported to increase the risk of diabetes about threefold and even more in patients without previous treatment with systemic steroids (Blackman et al, 2009). Variants of other genes are suspected to increase the risk of liver cirrhosis (Bartlett et al, 2009) or meconium ileus. Further progress in the identification of modifier genes should result in an increased ability to predict severity of CF disease, and hopefully be accompanied by new perspectives for therapeutic intervention.…”