ABCMdb

ABCC7 p.Gly1237Ala

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Publications

PMID: 12689922 [PubMed] Frangolias DD et al: "Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease."

No. Sentence Comment

82 Stepwise linear regression analysis was used to predict %change in ␣1-AT and parameters used included current age, sex, CF diagnosis age, CFTR genotype, TABLE 2 Clinical characteristics of study subjects stratified by ␣1-AT 3Ј G1237 →A genotype Total G1237G G1237A or A1237A P value Sex, M/F 379/337 331/283 48/54 0.20 Age, yr 22.8 (0.4) 22.7 (0.4) 23.5 (1.2) 0.49 CFTR genotype (⌬F508/⌬F508; ⌬F508/other; other/other) 391/296/72 343/244/60 48/52/12 0.14 Age of CF diagnosis, yr 4.7 (0.3) 4.6 (0.3) 5.4 (0.9) 0.38 %predFEV1 64.8 (0.9) 64.9 (1.0) 63.7 (2.3) 0.64 BMI, kg/m2 20.3 (0.2) 20.4 (0.2) 20.0 (0.4) 0.49 Pancreatic sufficiency status (sufficient/insufficient) 119/649 95/561 24/88 0.05 No. of P. aeruginosa-positive/not colonized 478/85 416/70 62/15 0.23 Age of first infection with P. aeruginosa 11.1 (0.5) 11.3 (0.5) 10.0 (1.1) 0.36 Age of chronic P. Aeruginosa infection 14.4 (0.8) 14.5 (0.9) 13.6 (1.6) 0.71 Frequency of intravenous treatment/yr 0.9 (0.1) 0.9 (0.1) 0.9 (0.2) 0.86 Days of intravenous treatment/yr 13.7 (1.2) 13.5 (1.6) 15.4 (4.5) 0.60 Dead or lung transplanted/alive 63/644 53/551 10/92 0.71 The study sample varied between 713 and 716 for univariate analyses. For analysis of age of first infection with P. aeruginosa and P. aeruginosa status, the study sample size was 461 and 555, respectively. For analysis of age of chronic infection with P. aeruginosa, the study sample was 159. Login to comment

PMID: 16207846 [PubMed] Drumm ML et al: "Genetic modifiers of lung disease in cystic fibrosis."

No. Sentence Comment

76 * Gene andReference†Variant‡ReferenceSNP Impairmentof LungFunctionGenotype Patientswith theGenotypeGenotype Patientswith theGenotypeGenotype Patientswith theGenotype Number ofPatients P Value§ %%% a1AP4-8Sallele17580SevereAA91.5AT8.5TT02601.00 (T2313A)MildAA91.4AT8.5TT0.2544 ZalleleNoneSevereGG96.0GA4.0AA02520.39 (G4627A)MildGG97.2GA2.8AA0529 3'enhancer11568814SevereGG85.8GA13.5AA0.82600.75 (G1237A)MildGG84.7GA14.7AA0.6544 ACE9DorIdeletionNASevereDD39.3DI39.3II21.42620.32 MildDD38.2DI44.7II17.1544 ADRb210(A46G)1042713SevereGG39.1GA48.5AA12.32350.62 MildGG41.7GA48.0AA10.3506 (C79G)1042714SevereCC26.8CG56.6GG16.62350.45 MildCC29.9CG51.6GG18.5508 GSTM111,13NulldeletionNASevereDD52.1--DN/NN47.92610.50 MildDD54.9--DN/NN45.1539 GSTP113(A1375G)947894SevereAA46.2AG44.2GG9.62600.81 MildAA44.0AG45.1GG10.9543 IL109(G-1082A)1800896SevereGG23.1GA55.4AA21.52600.96 MildGG24.1GA55.0AA21.0544 MBL214-18O¶NASevereAA59.5AO35.5OO5.02620.58 MildAA58.2AO37.5OO4.3536 XA/O¿NASevereOther85.8XA/O9.2O/O5.02621.00 MildOther85.6XA/O10.0O/O4.3536 NOS319T5220G1799983SevereGG43.5GT45.8TT10.82600.54 MildGG46.0GT41.7TT12.3544 TGFb19,20**Promoter1800469SevereCC43.8CT43.8TT12.32600.006 (C-509T)MildCC50.4CT43.8TT5.9544 Codon101982073SevereTT34.0TC46.3CC19.72590.0008 (C29T)††MildTT41.4TC48.4CC10.1543 Codon251800471SevereGG82.2GC17.4CC0.42590.06 (G74C)MildGG87.7GC11.6CC0.7544 TNFa9,12Promoter1800629SevereGG68.1GA29.0AA2.92380.91 (G-308A)MildGG68.7GA27.7AA3.6505 seen only for TGFb1 variants; the codon 10 variant hadamultiple-comparisoncorrectedPvalueof0.01 (the most significant association among the 16 in Table 2). Login to comment

PMID: 17033796 [PubMed] Buscher R et al: "Disease modifying genes in cystic fibrosis: therapeutic option or one-way road?"

No. Sentence Comment

39 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 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

PMID: 15996905 [PubMed] Slieker MG et al: "Disease modifying genes in cystic fibrosis."

No. Sentence Comment

102 Another polymorphism in the 3` non-coding region enhancer-binding element of the a1-AT gene (G1237A) may reduce the rise in the level of a1-antitrypsin during the acute phase response, whilst leaving baseline levels unaffected [33]. Login to comment
105 In the latter study, no association between the G1237A polymorphism and lung function was found. Login to comment
107 Finally, in a large recent Canadian study (n = 716), one of the few that adjusted for confounders, none of the associations between deficiency Z and S genotypes or G1237A polymorphisms, and lung function or age of P. aeruginosa colonization could be confirmed [37]. Login to comment