ABCMdb

PMID: 17033796

Buscher R, Grasemann H
Disease modifying genes in cystic fibrosis: therapeutic option or one-way road?
Naunyn Schmiedebergs Arch Pharmacol. 2006 Nov;374(2):65-77. Epub 2006 Oct 11., [PubMed]

Sentences

No. Mutations Sentence Comment

39 ABCC7 p.Gly1237Ala Disease severity Stanke et al. 2006 MIF (MIF chromosome 22q11) American, ethnicity unspecified 167 CF patients, 166 healthy controls CATT-repeat -794, promoter: MIF5+=39%, MIF5- =61% [CF] vs MIF5+=43%, MIF5- =57% [controls] 5-CATT repeat with lowest promoter activity 5-CATT allele: colonisation with P. aeruginosa ↓; risk for pancreatic insufficiency ↓ Plant et al. 2005 IL10 (IL10 chromosome 1q31-q32) French, German 378 CF patients SNP -1082 G/A, promoter:CF patients: -1082GG: 24.9%, -1,082AG: 49.7%, -1082AA:25.4% [IL10] ↑ -1082G: colonisation with Aspergillus fumigatus ↑; risk for ABPA↑ Brouard et al. 2005 GSTM1 + GSTM3 (GSTM1 + GSTM3 chromosome 1p13.3) British, ethnicity unspecified 53 CF patients GSTM1 gene deletion: 49% of study population GSTM1 deficient (GSTM1-0/0) No protein Chrispin-Norman X-ray score ↓; +Shwachman-score ↓ in GSTM1-0/0 Hull and Thomson 1998 French 146 CF patients, 147 healthy controls GSTM3 3 base pair deletion in intron 6: GSTM3, A/A=0.68, A/B=0.29, B/B=0.03 [CF] vs A/A=0.65, A/B=0.31, B/B=0.04 [controls] [GSTM3] ↑ B-allele carriers: FEV1 and FVC ↑ (influenced by GSTM1 genotype) Flamant et al. 2004 American and Canadian, ethnicity unspecified 440 CF patients Glutamate-cysteine ligase subunit (GCLC) TNR GAG repeats: 7/7 allele pair 40%; 7/8 allele pair 17%; 7/9 allele pair 28%; other 15% [GSH] ↑ CF patients with milder CFTR genotype show strong association with lung disease severity McKone et al. 2006 GSTP1 (GSTP1 chromosome 11q13) French 106 CF patients 105Ile/Val: Ile =0.7, Val=0.3, [CF]; Ile=0.83, Val=0.17 [CF with liver disease] vs Ile=0.66, Val=0.34 [CF without liver disease] [GSTP1] ↑ 105Ile/Ile: Risk for liver cirrhosis increased ↑ Henrion-Caude et al. 2002 Table 1 (continued) Gene Population Number Gene variant + frequency Biological effect Phenotype ReferenceGene variant + frequency ReferencePhenotypeBiological effect Population Number α1AT (α1AT chromosome 14q32.1) British 79 CF patients SNP, 3`G1237A, enhancer polymorphism: 2.5% heterozygous for S-allele, 5.1% heterozygous for Z-allele [α1AT] ↓ No association with lung function Mahadeva et al. 1998a,b Irish 124 CF patients SNP G1237A, 5' enhancer polymorphism: A=0.13, G =0.87 [α1AT] ↓ Brasfield X-ray score ↑ 1237A allele carriers with better pulmonary prognosis 1237A: chronic colonisation with P. aeruginosa ↓ Henry et al. 2001 Canadian 716 CF patients SNP, 3`G1237A, enhancer polymorphism: A=0.14, G =0.86 [α1AT] ↓ No association with more severe clinical outcome (death or lung transplantation) or age at onset of P. aeruginosa infection Frangolias et al. 2003 Danish 215 CF patients SNP, codon 264SNP G/A, codon 342 [α1-AT] ↓ Earlier colonisation with P. aeruginosa serum Pseudomonas-antibodies ↑ Döring et al. 1994 α1ACT (α1ACT chromosome 14q31-q31.2) British 157 CF patients, 45 healthy controls SNP -15 G/APromoter (-15 Thr→Ala): G=0.66, A=0.34 [CF] vs. Login to comment 108 ABCC7 p.Gly1237Ala The question of whether common α1AT alleles and polymorphisms such as Z and S deficiency alleles and the G1237A polymorphism are associated with CF disease severity has been investigated in a number of different studies that revealed inconsistent results (Mahadeva et al. 1998a,b; Henry et al. 2001; Frangolias et al. 2003; Döring et al. 1994; Table 1). Login to comment