Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial

被引:28
作者
Bodonyi-Kovacs, Gabor [1 ]
Ma, Jennie Z. [2 ]
Chang, Jamison [1 ]
Lipkowitz, Michael S. [3 ]
Kopp, Jeffrey B. [4 ]
Winkler, Cheryl Ann [5 ]
Le, Thu H. [1 ]
机构
[1] Univ Virginia, Dept Med, Div Nephrol, Charlottesville, VA USA
[2] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA
[3] Georgetown Univ, Dept Med, Div Nephrol, Washington, DC USA
[4] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA
[5] NCI, Basic Res Lab, Ctr Canc Res, NIH,Leidos Biomed Inc,Frederick Natl Lab, Frederick, MD 21701 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2016年 / 27卷 / 10期
基金
美国国家卫生研究院;
关键词
GENE POLYMORPHISM; VARIANTS; ASSOCIATION; GENOTYPE; DECLINE;
D O I
10.1681/ASN.2015050487
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
Apolipoprotein L-1 (APOL1) high risk alleles and the glutathione-S-transferase-mu 1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high or low risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m(2) decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P <= 0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups.
引用
收藏
页码:3140 / 3152
页数:13
相关论文
共 25 条
  • [1] Relationship between GSTs gene polymorphism and susceptibility to end stage renal disease among North Indians
    Agrawal, Suraksha
    Tripathi, Gaurav
    Khan, Faisal
    Sharma, Rajkumar
    Baburaj, Vinod Pandirikkal
    [J]. RENAL FAILURE, 2007, 29 (08) : 947 - 953
  • [2] [Anonymous], 2011, USRDS 2011 ANN DAT R
  • [3] GENETIC-HETEROGENEITY OF THE HUMAN GLUTATHIONE TRANSFERASES - A COMPLEX OF GENE FAMILIES
    BOARD, P
    COGGAN, M
    JOHNSTON, P
    ROSS, V
    SUZUKI, T
    WEBB, G
    [J]. PHARMACOLOGY & THERAPEUTICS, 1990, 48 (03) : 357 - 369
  • [4] Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: A literature-based systematic HuGE review and meta-analysis
    Carlsten, C.
    Sagoo, G. S.
    Frodsham, A. J.
    Burke, W.
    Higgins, J. P. T.
    [J]. AMERICAN JOURNAL OF EPIDEMIOLOGY, 2008, 167 (07) : 759 - 774
  • [5] Loss of GSTM1, a NRF2 target, is associated with accelerated progression of hypertensive kidney disease in the African American Study of Kidney Disease (AASK)
    Chang, Jamison
    Ma, Jennie Z.
    Zeng, Qing
    Cechova, Sylvia
    Gantz, Adam
    Nievergelt, Caroline
    O'Connor, Daniel
    Lipkowitz, Michael
    Le, Thu H.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2013, 304 (04) : F348 - F355
  • [6] Proteomic Analysis of Defined HDL Subpopulations Reveals Particle-Specific Protein Clusters Relevance to Antioxidative Function
    Davidson, W. Sean
    Silva, R. A. Gangani D.
    Chantepie, Sandrine
    Lagor, William R.
    Chapman, M. John
    Kontush, Anatol
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (06) : 870 - U234
  • [7] Gene-gene interactions in APOL1-associated nephropathy
    Divers, Jasmin
    Palmer, Nicholette D.
    Lu, Lingyi
    Langefeld, Carl D.
    Rocco, Michael V.
    Hicks, Pamela J.
    Murea, Mariana
    Ma, Lijun
    Bowden, Donald W.
    Freedman, Barry I.
    [J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 2014, 29 (03) : 587 - 594
  • [8] JC polyoma virus interacts with APOL1 in African Americans with nondiabetic nephropathy
    Divers, Jasmin
    Nunez, Marina
    High, Kevin P.
    Murea, Mariana
    Rocco, Michael V.
    Ma, Lijun
    Bowden, Donald W.
    Hicks, Pamela J.
    Spainhour, Mitzie
    Ornelles, David A.
    Kleiboeker, Steven B.
    Duncan, Kara
    Langefeld, Carl D.
    Turner, JoLyn
    Freedman, Barry I.
    [J]. KIDNEY INTERNATIONAL, 2013, 84 (06) : 1207 - 1213
  • [9] APOL1 Kidney Disease Risk Variants: An Evolving Landscape
    Dummer, Patrick D.
    Limou, Sophie
    Rosenberg, Avi Z.
    Heymann, Jurgen
    Nelson, George
    Winkler, Cheryl A.
    Kopp, Jeffrey B.
    [J]. SEMINARS IN NEPHROLOGY, 2015, 35 (03) : 222 - 236
  • [10] Lipid biology of the podocyte-new perspectives offer new opportunities
    Fornoni, Alessia
    Merscher, Sandra
    Kopp, Jeffrey B.
    [J]. NATURE REVIEWS NEPHROLOGY, 2014, 10 (07) : 379 - 388