臨床泌尿器科60巻1号

2006年01月発行

綜説

腎移植と遺伝子多型

著者： 佐藤滋²

所属機関： ²秋田大学医学部泌尿器科

ページ範囲：P.7 - P.15

文献概要

癌の発症・進展，代謝疾患や薬剤応答などさまざまな領域で遺伝子多型解析を用いた研究が行われている。腎移植領域でも，移植腎機能発現遅延，急性拒絶，慢性移植腎症や生着率・予後，免疫抑制剤に対する応答，移植後糖尿病などの合併症といった臨床事象と遺伝子多型との関連についての研究報告が，急速に増加している。一連の研究成果は様々な臨床事象の原因究明の一助になるとともに，個別化治療への新たなアプローチの一つとして期待される。本稿では，腎移植領域における遺伝子多型解析を用いた最近の報告を，筆者らの研究も含めて紹介する。

参考文献

1）Habuchi T, Suzuki T, Sasaki R, et al：Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population. Cancer Res 60：305-308, 2000

2）Habuchi T, Wang LZ, Suzuki T, et al：Increased risk of prostate cancer and benign prostatic hyperplasia accociated with a CYP17gene polymorphism with a gene dosage effect. Cancer Res 60：5710-5713, 2000

3）Wang LZ, Tsuchiya N, Sato K, et al：Polymorphisms in prostate-specific antigen（PSA）gene, risk of prostate cancer, and serum PSA levels in Japanese population. Cancer Lett 202：53-59, 2003

4）Narita S, Tsuchiya N, Wang LZ, et al：Association of lipoprotein lipase gene polymorphism with risk of prostate cancer in a Japanese population. Int J Cancer 112：872-876, 2004

5）Alakulppi NS, Kyllonen LE, Jantti VT, et al：Cytokine gene polymorphisms and risks of acute rejection and delayed graft function after kidney transplantation. Transplantation 78：1422-1428, 2004

6）Mange KC, Prak EL, Kamoun M, et al：Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function. Kidney Int 66：1187-1192, 2004

7）St Peter SD, Imber CJ, Jones DC, et al：Genetic determinants of delayed graft function after kidney transplantation. Transplantation 74：809-813, 2002

8）Tinckam K, Rush D, Hutchinson I, et al：The relative importance of cytokine gene polymorphisms in the development of early and late acute rejection and six-month renal allograft pathology. Transplantation 79：836-841, 2005

9）Hoffmann S, Park J, Jacobson LM, et al：Donor genomic influence graft events：the effect of donor polymorphisms on acute rejection and chronic allograft nephropathy. Kidney Int 66：1686-1693, 2004

10）Lee H, Clark B, Gooi HC, et al：Influence of recipient and donor IL-1α, IL-4, and TNFαgenotypes on the incidence of acute allograft rejection. J Clin Pathol 57：101-103, 2004

11）Loucaidou M, Stitchbury J, Lee J, et al：Cytokine polymorphisms do not influence acute rejection in renal transplantation under tacrolimus-based immunosuppression. Transplant Proc 37：1760-1761, 2005

12）Cappellesso S, Valentin JF, Giraudea B, et al：Association of donor TNFGSF6（FAS）gene polymorphism with acute rejection in renal transplant patients：a case control study. Nphrol Dial Transplant 19：439-443, 2004

13）Yuan FF, Watson N, Sullivan JS, et al：Association of Fc gamma receptorⅡA polymorphisms with acute renal-allograft rejection. Transplantation 78：766-769, 2004

14）Kabat-Koperska J, Baskiewicz-Masiuk M, Safranow K, et al：The influence of angiotensin-converting enzyme gene of donor and recipient on the function of transplanted kidney. Transplant Proc 37：755-759, 2005

15）Chow KM, Szeto CC, Szeto CY, et al：Plasminogen activator inhibitor-1 polymorphism is associated with progressive renal dysfunction after acute rejection in renal transplant recipients. Transplantation 74：1791-1794, 2000

16）Kruger B, Schroppel B, Ashkan R, et al：A monocyte chemoattractant protein-1（MCP-1）polymorphism and outome after renal transplantation. J Am Soc Nephrol 13：2585-2589, 2002

17）Lemos FB, Mol WM, Roodnat JI, et al：The beneficial effects of recipient-derived vascular endothelial growth factor on graft survival after kidney transplantation. Transplantation 79：1221-1225, 2005

18）Pawlik A, Domanski L, Rozanski J, et al：The cytokine gene polymorphisms in patients with chronic kidney graft rejection. Transplant Immunol 14：49-52, 2005

19）Muller-Steinhardt M, Fricke L, Muller B, et al：Cooperative influence of the interleukin-6 promoter polymorphisms-597, 572 and-174 on long-term kidney allograft survival. Am J Transplant 4：402-406, 2004

20）Viklicky O, Hubacek JA, Kvasnicka J, et al：Association of methylenetetrahydrofolate reductase T677 allele with early development of chronic allograft nephropathy. Clin Biochem 37：919-924, 2004

21）Exner M, Bohming GA, Schillinger M, et al：Donor heme oxygenase-1genotype is associated with renal allograft function. Transplantation 77：538-542, 2004

22）Akcay A, Sezer S, Ozdemir FN, et al：Association of the genetic polymorphisms of the renin-angiotensin system and endothelial nitric oxide synthase with chronic renal transplant dysfunction. Transplantation 78：892-898, 2004

23）Reis K, Arinsoy T, Derici U, et al：Angiotensinogen and plasminogen activator inhibitor-1gene polymorphism in relation to chronic allograft dysfunction. Clin Transplant 19：10-14, 2005

24）加藤隆一：薬理遺伝学の歴史と発展．澤田康文（編）：薬物動態・作用と遺伝子多型．医薬ジャーナル社，大阪，pp14-23，2001

25）立石智則：CYP1A2，2A6，2E1，3A．澤田康文（編）：薬物動態・作用と遺伝子多型．医薬ジャーナル社，大阪，pp147-157，2001

26）大谷壽一，澤田康文：MDR1．澤田康文（編）：薬物動態・作用と遺伝子多型．医薬ジャーナル社，大阪，pp265-275，2001

27）Hesselink DA, van Gelder T, van Schaik RH, et al：Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5genes. Clin Pharmacol Ther 76：545-556, 2004

28）Yates CR, Zhang W, Song P, et al：The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol 43：555-564, 2003

29）Haufroid V, Mourad M, van Kerckhove, et al：The effect of CYP3A5 and MDR1（ABCB1）polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 14：147-154, 2004

30）Hesselink DA, van Schaik RH, van der Heiden IP, et al：Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 74：245-254, 2003

31）Anglicheau D, Thervet E, Etienne I, et al：CYP3A5 and MDR1genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin Pharmacol Ther 75：422-433, 2004

32）Hauser IA, Schaeffeler E, Gauer S, et al：ABCB1genotype of the donor but not of the recipient is a major risk factor for cyclosporine-related nephrotoxicity after renal transplantation. J Am Soc Nephrol 16：1501-1511, 2005

33）Tsuchiya N, Satoh S, Tada H, et al：Influence of CYP3A5 and MDR1（ABCB1）polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation 78：1182-1187, 2004

34）Tada H, Tsuchiya N, Satoh S, et al：Impact of CYP3A5 and MDR1（ABCB1）C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplant Proc 37：1730-1732, 2005

35）Satoh S, Tada H, Murakami M, et al：The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation. Transplant Proc 37：1751-1753, 2005

36）Satoh S, Tada H, Murakami M, et al：Circadian pharmacokinetics of mycophenolic acid and implication of genetic polymorphisms for early clinical events in renal transplant recipients. Transplantation（in printing）

37）Miura M, Kagaya H, Tada H, et al：Comparison of enantioselective disposition of rabeprazole versus lansoprazole in renal-transplant recipients who are CYP2C19 extensive metabolizers. Xenobiotica 35：479-486, 2005

38）Altun B, Yilmaz R, Kahraman S, et al：Impact of cytokine gene polymorphism on cardiovascular risk in renal transplant recipients. Transplant Int 18：681-689, 2005

39）Babel N, Cherepnev G, Kowalenko A, et al：Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants. Kidney Int 66：428-432, 2004

40）Numakura K, Satoh S, Tsuchiya N, et al：Incidence and risk factors of clinical characteristics, tacrolimus pharmacokinetics, and related genomic polymorphisms for posttransplant diabetes mellitus in the early stage of renal transplant recipients. Transplant Proc 37：1865-1867, 2005

41）Numakura K, Satoh S, Tsuchiya N, et al：Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus. Transplantation 80：1419-1424, 2005

42）Satoh S, Kaneko T, Seino K, et al：Angiotensin-converting enzyme inhibitor-induced anemia and treatment for erythrocytosis in renal transplant recipients. Nippon Jinzo Gakkai Shi 37：343-347, 1995

43）Micozkadioglu H, Colak T, Akcay A, et al：Angiotensin-converting enzyme gene polymorphism significantly affects renal posttransplant erythro-cytosis. Transplant Proc 36：161-163, 2004

44）Asano T, Takahasi KA, Fujioka M, et al：Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation 27：220-225, 2004