CC-chemokine receptor five gene polymorphism in primary IgA nephropathy: The 32 bp deletion allele is associated with late progression to end-stage renal failure with dialysis

被引:20
作者
Berthoux, FC [1 ]
Berthoux, P
Mariat, C
Thibaudin, L
Afiani, A
Linossier, MT
机构
[1] CHU St Etienne, Univ N Hosp, Nephrol Dialysis & Renal Translantat Dept, F-42055 St Etienne 2, France
[2] Fac Med, Res Grp Glomerulonephritides & Renal Transplantat, St Etienne, France
关键词
IgA nephropathy; gene polymorphism; chemokine receptor five (CCR5); disease initiation; disease progression; prognostic markers;
D O I
10.1038/sj.ki.5000106
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The chemokine (CK) receptor 5 (CCR5) is necessary for two adjacent cysteines (CC)-CKs such as Regulated upon Activation Normal T cell Expressed and Secreted, a/o Macrophage Inflammatory Protein 1 alpha/beta to mediate their inflammatory properties. The CCR5 gene polymorphism with 32-basepair deletion (d32) leads to receptor inactivation/dysfunction in homo/heterozygous individuals. We have evaluated its role in both initiation and/or progression of primary immunoglobulin A (IgA) nephropathy (IGAN) in a case-control study involving a prospective cohort of 318 IGAN patients and a matched group of 294 controls. Genotyping was performed by a two-specific primers single polymerase chain reaction technique: normal allele (nl) vs d32 allele. The d32 allele frequency was not different in patients (11.0%) vs controls (8.3%), indicating no significant influence on IGAN initiation. Genotype to clinical phenotype correlation demonstrated that progression to renal/patient death was associated with the d32 allele: 18.2% (12 out of 66 with d32) vs 8.3% (21 out of 252); chi(2) = 6.73; P = 0.017. The Kaplan-Meier survival without renal/patient death was worse in d32-positive patients (log-rank test; P = 0.002). The Cox regression analyses confirmed that the nl/nl genotype was a significant and independent protective factor for progression to end-stage renal failure (ESRF)/dialysis: beta/standard error (s.e.) = -3.1; chi(2) = 9.5; relative risk 0.31 (95% confidence interval 0.15-0.65); P = 0.002. The d32-CCR5 polymorphism played a significant role in the progression of primary IGAN, with the nl/nl genotype being an independent protective factor for late progression towards ESRF/dialysis. These data raise question about the usefulness of systematic CCR5 genotyping in IGAN patients.
引用
收藏
页码:565 / 572
页数:8
相关论文
共 37 条
[1]  
Aguilar F, 2003, J RHEUMATOL, V30, P1770
[2]  
ALAMARTINE E, 1990, CLIN NEPHROL, V34, P45
[3]   PROGNOSTIC FACTORS IN MESANGIAL IGA GLOMERULONEPHRITIS - AN EXTENSIVE STUDY WITH UNIVARIATE AND MULTIVARIATE ANALYSES [J].
ALAMARTINE, E ;
SABATIER, JC ;
GUERIN, C ;
BERLIET, JM ;
BERTHOUX, F .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1991, 18 (01) :12-19
[4]   CC chemokine ligand 5/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration [J].
Anders, HJ ;
Frink, M ;
Linde, Y ;
Banas, B ;
Wörnle, M ;
Cohen, CD ;
Vielhauer, V ;
Nelson, PJ ;
Gröne, HJ ;
Schlöndorff, D .
JOURNAL OF IMMUNOLOGY, 2003, 170 (11) :5658-5666
[5]   Chemokines and chemokine receptors are involved in the resolution or progression of renal disease [J].
Anders, HJ ;
Vielhauer, V ;
Schlöndorff, D .
KIDNEY INTERNATIONAL, 2003, 63 (02) :401-415
[6]  
[Anonymous], 2002, Am J Kidney Dis
[7]   Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis [J].
Bonnet, F ;
Deprele, C ;
Sassolas, A ;
Moulin, P ;
Alamartine, E ;
Berthezène, F ;
Berthoux, F .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2001, 37 (04) :720-727
[8]   Population stratification and spurious allelic association [J].
Cardon, LR ;
Palmer, LJ .
LANCET, 2003, 361 (9357) :598-604
[9]   Problems of reporting genetic associations with complex outcomes [J].
Colhoun, HM ;
McKeigue, PM ;
Smith, GD .
LANCET, 2003, 361 (9360) :865-872
[10]   Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 alpha, MIP-1 beta, and RANTES [J].
Combadiere, C ;
Ahuja, SK ;
Tiffany, HL ;
Murphy, PM .
JOURNAL OF LEUKOCYTE BIOLOGY, 1996, 60 (01) :147-152