Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals

被引:9
作者
Horibe, Hideki [1 ]
Fujimaki, Tetsuo [2 ]
Oguri, Mitsutoshi [3 ]
Kato, Kimihiko [4 ,5 ]
Matsuoka, Reiko [6 ]
Abe, Shintaro [6 ]
Tokoro, Fumitaka [6 ]
Arai, Masazumi [6 ]
Noda, Toshiyuki [6 ]
Watanabe, Sachiro [6 ]
Yamada, Yoshiji [5 ]
机构
[1] Gifu Prefectural Tajimi Hosp, Dept Cardiovasc Med, Tajimi, Japan
[2] Inabe Gen Hosp, Dept Cardiovasc Med, Inabe, Japan
[3] Japanese Red Cross Nagoya First Hosp, Dept Cardiol, Nagoya, Aichi, Japan
[4] Meitoh Hosp, Dept Internal Med, Nagoya, Aichi, Japan
[5] Mie Univ, Dept Human Funct Genom, Life Sci Res Ctr, Tsu, Mie 5148507, Japan
[6] Gifu Prefectural Gen Med Ctr, Dept Cardiol, Gifu, Japan
关键词
genetics; interleukin-6; kidney failure; polymorphism; receptors; renal insufficiency; SUSCEPTIBILITY LOCI; EXPRESSION; VARIANTS; IDENTIFICATION; INFLAMMATION; HEART; IL6R;
D O I
10.1111/nep.12381
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
AimVarious loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs. MethodsThe study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60mLmin(-1) 1.73m(-2)] and 659 controls (eGFR of 90mLmin(-1) 1.73m(-2)). The genotypes for 29 polymorphisms of 28 candidate genes were determined. ResultsThe (2) test revealed that rs4845625 (TC) of IL6R, rs4773144 (AG) of COL4A1, rs9319428 (GA) of FLT1, and rs46522 (TC) of UBE2Z were significantly (P<0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P=0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P=0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P=0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P=0.0065) greater and eGFR was significantly (P=0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype. ConclusionThe rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals. Summary at a Glance The authors detected a novel SNP in the IL6R gene that correlates with CKD in a reasonably large Japanese cohort.
引用
收藏
页码:273 / 278
页数:6
相关论文
共 31 条
  • [1] Large-scale association analysis identifies new risk loci for coronary artery disease
    Deloukas, Panos
    Kanoni, Stavroula
    Willenborg, Christina
    Farrall, Martin
    Assimes, Themistocles L.
    Thompson, John R.
    Ingelsson, Erik
    Saleheen, Danish
    Erdmann, Jeanette
    Goldstein, Benjamin A.
    Stirrups, Kathleen
    Koenig, Inke R.
    Cazier, Jean-Baptiste
    Johansson, Asa
    Hall, Alistair S.
    Lee, Jong-Young
    Willer, Cristen J.
    Chambers, John C.
    Esko, Tonu
    Folkersen, Lasse
    Goel, Anuj
    Grundberg, Elin
    Havulinna, Aki S.
    Ho, Weang K.
    Hopewell, Jemma C.
    Eriksson, Niclas
    Kleber, Marcus E.
    Kristiansson, Kati
    Lundmark, Per
    Lyytikainen, Leo-Pekka
    Rafelt, Suzanne
    Shungin, Dmitry
    Strawbridge, Rona J.
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    Van Zuydam, Natalie
    Voight, Benjamin F.
    Waite, Lindsay L.
    Zhang, Weihua
    Ziegler, Andreas
    Absher, Devin
    Altshuler, David
    Balmforth, Anthony J.
    Barroso, Ines
    Braund, Peter S.
    Burgdorf, Christof
    Claudi-Boehm, Simone
    Cox, David
    Dimitriou, Maria
    Do, Ron
    [J]. NATURE GENETICS, 2013, 45 (01) : 25 - U52
  • [2] Di Lullo L., 2014, Heart failure reviews
  • [3] K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification - Foreword
    Eknoyan, G
    Levin, NW
    [J]. AMERICAN JOURNAL OF KIDNEY DISEASES, 2002, 39 (02) : S14 - S266
  • [4] Identification of IL6R and chromosome 11q13.5 as risk loci for asthma
    Ferreira, Manuel A. R.
    Matheson, Melanie C.
    Duffy, David L.
    Marks, Guy B.
    Hui, Jennie
    Le Souef, Peter
    Danoy, Patrick
    Baltic, Svetlana
    Nyholt, Dale R.
    Jenkins, Mark
    Hayden, Catherine
    Willemsen, Gonneke
    Ang, Wei
    Kuokkanen, Mikko
    Beilby, John
    Cheah, Faang
    de Geus, Eco J. C.
    Ramasamy, Adaikalavan
    Vedantam, Sailaja
    Salomaa, Veikko
    Madden, Pamela A.
    Heath, Andrew C.
    Hopper, John L.
    Visscher, Peter M.
    Musk, Bill
    Leeder, Stephen R.
    Jarvelin, Marjo-Riitta
    Pennell, Craig
    Boomsma, Dorret I.
    Hirschhorn, Joel N.
    Walters, Haydn
    Martin, Nicholas G.
    James, Alan
    Jones, Graham
    Abramson, Michael J.
    Robertson, Colin F.
    Dharmage, Shyamali C.
    Brown, Matthew A.
    Montgomery, Grant W.
    Thompson, Philip J.
    [J]. LANCET, 2011, 378 (9795) : 1006 - 1014
  • [5] INCREASED SYNTHESIS OF EXTRACELLULAR-MATRIX IN MESANGIAL PROLIFERATIVE NEPHRITIS
    FLOEGE, J
    JOHNSON, RJ
    GORDON, K
    IIDA, H
    PRITZL, P
    YOSHIMURA, A
    CAMPBELL, C
    ALPERS, CE
    COUSER, WG
    [J]. KIDNEY INTERNATIONAL, 1991, 40 (03) : 477 - 488
  • [6] Genetics of kidney failure and the evolving story of APOL1
    Friedman, David J.
    Pollak, Martin R.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (09) : 3367 - 3374
  • [7] Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization
    Go, AS
    Chertow, GM
    Fan, DJ
    McCulloch, CE
    Hsu, CY
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (13) : 1296 - 1305
  • [8] Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC
    Gupta, Jayanta
    Mitra, Nandita
    Kanetsky, Peter A.
    Devaney, Joe
    Wing, Maria R.
    Reilly, Muredach
    Shah, Vallabh O.
    Balakrishnan, Vaidyanathapura S.
    Guzman, Nicolas J.
    Girndt, Matthias
    Periera, Brian G.
    Feldman, Harold I.
    Kusek, John W.
    Joffe, Marshall M.
    Raj, Dominic S.
    [J]. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 7 (12): : 1938 - 1946
  • [9] Glomerular expression of type IV collagen chains in normal and X-linked Alport syndrome kidneys
    Heidet, L
    Cai, Y
    Guicharnaud, L
    Antignac, C
    Gubler, MC
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (06) : 1901 - 1910
  • [10] Principles of interleukin (IL)-6-type cytokine signalling and its regulation
    Heinrich, PC
    Behrmann, I
    Haan, S
    Hermanns, HM
    Müller-Newen, G
    Schaper, F
    [J]. BIOCHEMICAL JOURNAL, 2003, 374 (01) : 1 - 20