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01.08.2014 | Original Article—ALIMENTARY TRACT

Characteristics of Japanese inflammatory bowel disease susceptibility loci

verfasst von: Yoshiaki Arimura, Hiroyuki Isshiki, Kei Onodera, Kanna Nagaishi, Kentaro Yamashita, Tomoko Sonoda, Takayuki Matsumoto, Atsushi Takahashi, Masakazu Takazoe, Keiko Yamazaki, Michiaki Kubo, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura

Erschienen in: Journal of Gastroenterology | Ausgabe 8/2014

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Abstract

Background

There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD.

Methods

For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn’s disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls.

Results

We confirmed that the NKX2–3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24).

Conclusions

Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

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Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573–621.PubMedCrossRef

Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006;41:10–6.PubMedCrossRef

Kuwahara E, Asakura K, Nishiwaki Y, Inoue N, Watanabe M, Hibi T, et al. Effect of family history on inflammatory bowel disease characteristics in Japanese patients. J Gastroenterol. 2012;47:961–8.PubMedCrossRef

Van Limbergen J, Russell RK, Nimmo ER, Satsangi J. The genetics of inflammatory bowel disease. Am J Gastroenterol. 2007;102:2820–31.PubMedCrossRef

Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet. 2007;39:830–2.PubMedCentralPubMedCrossRef

Silverberg MS, Cho JH, Rioux JD, McGovern DP, Wu J, Annese V, et al. Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet. 2009;41:216–20.PubMedCentralPubMedCrossRef

Franke A, Balschun T, Sina C, Ellinghaus D, Häsler R, Mayr G, et al. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Nat Genet. 2010;42:292–4.PubMedCrossRef

Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–24.PubMedCentralPubMedCrossRef

Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.PubMedCrossRef

10.

Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.PubMedCrossRef

11.

Steinman L. A brief history of Th17, the first major revision in the Th1/Th2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007;13:139–45.PubMedCrossRef

12.

Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223–8.PubMedCrossRef

13.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL-23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.PubMedCrossRef

14.

Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, et al. Lack of common NOD2 variants in Japanese patients with Crohn’s disease. Gastroenterology. 2002;123:86–91.PubMedCrossRef

15.

Yamazaki K, Takazoe M, Tanaka T, Ichimori T, Saito S, Iida A, et al. Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. J Hum Genet. 2004;49:664–8.PubMedCrossRef

16.

Yamazaki K, Onouchi Y, Takazoe M, Kubo M, Nakamura Y, Hata A. Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with Crohn’s disease in Japanese patients. J Hum Genet. 2007;52:575–83.PubMedCrossRef

17.

Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet. 2005;14:3499–506.PubMedCrossRef

18.

Asano K, Matsushita T, Umeno J, Hosono N, Takahashi A, Kawaguchi T, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet. 2009;41:1325–9.PubMedCrossRef

19.

Okada Y, Yamazaki K, Umeno J, Takahashi A, Kumasaka N, Ashikawa K, et al. HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn’s disease. Gastroenterology. 2011;141:864–71.PubMedCrossRef

20.

Yamazaki K, Umeno J, Takahashi A, Hirano A, Johnson TA, Kumasaka N, et al. A genome-wide association study identifies 2 susceptibility loci for Crohn’s disease in a Japanese population. Gastroenterology. 2013;144:781–8.PubMedCrossRef

21.

Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.PubMedCentralPubMedCrossRef

22.

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.PubMedCentralPubMedCrossRef

23.

Wang Z, Hu J, Fan R, Zhou J, Zhong J. Association between CD14 gene C-260T polymorphism and inflammatory bowel disease: a meta-analysis. PLoS ONE. 2012;7:e45144.PubMedCentralPubMedCrossRef

24.

Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, et al. Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis. 2008;14:437–45.PubMedCrossRef

25.

Tanaka M, Arimura Y, Goto A, Hosokawa M, Nagaishi K, Yamashita K, et al. Genetic variants in surfactant, pulmonary-associated protein D (SFTPD) and Japanese susceptibility to ulcerative colitis. Inflamm Bowel Dis. 2009;15:918–25.PubMedCrossRef

26.

Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6.PubMedCrossRef

27.

Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J. A method for meta-analysis of molecular association studies. Stat Med. 2005;24:1291–306.PubMedCrossRef

28.

Breslow NE, Day NE. Statistical methods in cancer research. Volume 1—the analysis of case–control studies. Lyon, UK International Agency for Research on Cancer. IARC Sci Publ. 1980;32:5–338.PubMed

29.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCentralPubMedCrossRef

30.

Weir BS. Genetic data analysis II. Sunderland: Sinauer Associates; 1996.

31.

Arai T, Kakuta Y, Kinouchi Y, Kimura T, Negoro K, Aihara H, et al. Increased expression of NKX2.3 mRNA transcribed from the risk haplotype for ulcerative colitis in the involved colonic mucosa. Hum Immunol. 2011;72:587–91.PubMedCrossRef

32.

Yamazaki K, Takahashi A, Takazoe M, Kubo M, Onouchi Y, Fujino A, et al. Positive association of genetic variants in the upstream region of NKX2-3 with Crohn’s disease in Japanese patients. Gut. 2009;58:228–32.PubMedCrossRef

33.

Nakagome S, Takeyama Y, Mano S, Sakisaka S, Matsui T, Kawamura S, et al. Population-specific susceptibility to Crohn’s disease and ulcerative colitis; dominant and recessive relative risks in the Japanese population. Ann Hum Genet. 2010;74:126–36.PubMedCrossRef

34.

Kakuta Y, Kinouchi Y, Negoro K, Takahashi S, Shimosegawa T. Association study of TNFSF15 polymorphisms in Japanese patients with inflammatory bowel disease. Gut. 2006;55:1527–8.PubMedCentralPubMedCrossRef

35.

Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher SA, Redon R, et al. Independent and population-specific association of risk variants at the IRGM locus with Crohn’s disease. Hum Mol Genet. 2010;19:1828–39.PubMedCentralPubMedCrossRef

36.

Hayashi R, Tahara T, Shiroeda H, Saito T, Nakamura M, Tsutsumi M, et al. Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis. Clin Exp Med. 2012;. doi:10.1007/s10238-012-0206-5.

37.

Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008;28:44–9.PubMedCrossRef

38.

Takagawa T, Tamura K, Takeda N, Tomita T, Ohda Y, Fukunaga K, et al. Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population. Inflamm Bowel Dis. 2005;11:1038–43.PubMedCrossRef

39.

Tamura K, Fukuda Y, Sashio H, Takeda N, Bamba H, Kosaka T, et al. IL18 polymorphism is associated with an increased risk of Crohn’s disease. J Gastroenterol. 2002;37:111–6.PubMedCrossRef

40.

Sashio H, Tamura K, Ito R, Yamamoto Y, Bamba H, Kosaka T, et al. Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectively. Immunogenetics. 2002;53:1020–7.PubMedCrossRef

41.

Negoro K, Kinouchi Y, Hiwatashi N, Takahashi S, Takagi S, Satoh J, et al. Crohn’s disease is associated with novel polymorphisms in the 5′-flanking region of the tumor necrosis factor gene. Gastroenterology. 1999;117:1062–8.PubMedCrossRef

42.

Matsuoka M, Sudo S, Nakamura M, Sugisaka H, Negishi M, Miyakawa Y, et al. Genetic association analysis of TNF-α and CD14 gene polymorphism with inflammatory bowel disease. Jpn J Gastroenterol. 2003;100(Suppl):A711 (in Japanese).

43.

Aoyagi Y, Nagata S, Kudo T, Fujii T, Wada M, Chiba Y, et al. Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis. Pediatr Int. 2010;52:729–34.PubMedCrossRef

44.

Wang F, Tahara T, Arisawa T, Sakata M, Takahama K, Watanabe M, et al. Polymorphism of peroxisome proliferator-activated receptor gamma is not associated to Japanese ulcerative colitis. Hepatogastroenterology. 2008;55:73–5.PubMed

45.

Sato K, Shiota M, Fukuda S, Iwamoto E, Machida H, Inamine T, et al. Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn’s disease in the Japanese population. J Clin Immunol. 2009;29:815–25.PubMedCentralPubMedCrossRef

46.

Machida H, Tsukamoto K, Wen CY, Narumi Y, Shikuwa S, Isomoto H, et al. Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese. World J Gastroenterol. 2005;11:4188–93.PubMed

47.

Matsuzawa J, Sugimura K, Matsuda Y, Takazoe M, Ishizuka K, Mochizuki T, et al. Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population. Gut. 2003;52:75–8.PubMedCentralPubMedCrossRef

48.

Narumi Y, Isomoto H, Shiota M, Sato K, Kondo S, Machida H, et al. Polymorphisms of PTPN11 coding SHP-2 as biomarkers for ulcerative colitis susceptibility in the Japanese population. J Clin Immunol. 2009;29:303–10.PubMedCrossRef

49.

Osuga T, Sakaeda T, Nakamura T, Yamada T, Koyama T, Tamura T, et al. MDR1 C3435T polymorphism is predictive of later onset of ulcerative colitis in Japanese. Biol Pharm Bull. 2006;29:324–9.PubMedCrossRef

50.

Kosaka T, Yoshino J, Inui K, Wakabayashi T, Okushima K, Kobayashi T, et al. Association between SHMT gene polymorphisms and ulcerative colitis. Jpn J Gastroenterol. 2009;106(Suppl):A826 (in Japanese).

51.

Shiroeda H, Tahara T, Nakamura M, Shibata T, Nomura T, Yamada H, et al. Association between functional promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene and ulcerative colitis in Japan. Cytokine. 2010;51:173–7.PubMedCrossRef

52.

Nohara H, Okayama N, Inoue N, Koike Y, Fujimura K, Suehiro Y, et al. Association of the −173 G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis. J Gastroenterol. 2004;39:242–6.PubMedCrossRef

53.

Fuse K, Katakura K, Sakamoto N, Ohira H. Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients. World J Gastroenterol. 2010;16:5815–21.PubMedCentralPubMedCrossRef

54.

Wang F, Tahara T, Arisawa T, Shibata T, Nakamura M, Fujita H, et al. Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. J Gastroenterol Hepatol. 2007;22:925–9.PubMedCrossRef

55.

Obana N, Takahashi S, Kinouchi Y, Negoro K, Takagi S, Hiwatashi N, et al. Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene, CD14. Scand J Gastroenterol. 2002;37:699–704.PubMedCrossRef

56.

Oomori S. Association between polymorphisms in the inhibitor of Kappa B-like protein (IKBL) gene and ulcerative colitis in a Japanese population. Med J Sendai Red Cross Hosp. 2009;18:23–32 (in Japanese).

57.

Aizawa H, Kinouchi Y, Negoro K, Nomura E, Imai G, Takahashi S, et al. HLA-B is the best candidate of susceptibility genes in HLA for Japanese ulcerative colitis. Tissue Antigens. 2009;73:569–74.PubMedCrossRef

58.

Kinouchi Y, Matsumoto K, Negoro K, Takagi S, Takahashi S, Hiwatashi N, et al. HLA-B genotype in Japanese patients with Crohn’s disease. Dis Colon Rectum. 2003;46:S10–4.PubMed

59.

Seki SS, Sugimura K, Ota M, Matsuzawa J, Katsuyama Y, Ishizuka K, et al. Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese. Tissue Antigens. 2001;58:71–6.PubMedCrossRef

60.

Futami S, Aoyama N, Honsako Y, Tamura T, Morimoto S, Nakashima T, et al. HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression. Dig Dis Sci. 1995;40:814–8.PubMedCrossRef

61.

Matsumura Y, Kinouchi Y, Nomura E, Negoro K, Kakuta Y, Endo K, et al. HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis. Tissue Antigens. 2008;71:447–52.PubMedCrossRef

62.

Tremelling M, Berzuini C, Massey D, Bredin F, Price C, Dawson C, et al. Contribution of TNFSF15 gene variants to Crohn’s disease susceptibility confirmed in UK population. Inflamm Bowel Dis. 2008;14:733–7.PubMedCrossRef

63.

Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, et al. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology. 2008;135:552–67.PubMedCentralPubMedCrossRef

64.

Lawrence PA, Morata G. Homeobox genes: their function in Drosophila segmentation and pattern formation. Cell. 1994;78:181–9.PubMedCrossRef

65.

Buchberger A, Pabst O, Brand T, Seidl K, Arnold HH. Chick NKx-2.3 represents a novel family member of vertebrate homologues to the Drosophila homeobox gene tinman: differential expression of cNKx-2.3 and cNKx-2.5 during heart and gut development. Mech Dev. 1996;56:151–63.PubMedCrossRef

66.

Fu Y, Yan W, Mohun TJ, Evans SM. Vertebrate tinman homologues XNk2–3 and XNk2–5 are required for heart formation in a functionally redundant manner. Development. 1998;125:4439–49.PubMed

67.

Wang CC, Biben C, Robb L, Nassir F, Barnett L, Davidson NO, et al. Homeodomain factor Nk2–3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. Dev Biol. 2000;224:152–67.PubMedCrossRef

68.

Pabst O, Förster R, Lipp M, Engel H, Arnold HH. NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue. EMBO J. 2000;19:2015–23.PubMedCentralPubMedCrossRef

69.

Stokkers PC, Reitsma PH, Tytgat GN, van Deventer SJ. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis. Gut. 1999;45:395–401.PubMedCentralPubMedCrossRef

70.

Ahmad T, Marshall SE, Jewell D. Genetics of inflammatory bowel disease: the role of the HLA complex. World J Gastroenterol. 2006;12:3628–35.PubMed

71.

Yang SK, Hong M, Zhao W, Jung Y, Baek J, Tayebi N, et al. Genome-wide association study of Crohn’s disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. Gut. 2013;. doi:10.1136/gutjnl-2013-305193.

72.

Ng SC, Tsoi KK, Kamm MA, Xia B, Wu J, Chan FK, et al. Genetics of inflammatory bowel disease in Asia: systematic review and meta-analysis. Inflamm Bowel Dis. 2012;6:1164–76.CrossRef

73.

Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, et al. Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008;40:713–5.PubMedCrossRef

74.

International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Ulcerative colitis meta-analysis summary statistics. http://www.ibdgenetics.org/downloads.html.

75.

Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, Plenge RM, et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet. 2008;4:e1000024.PubMedCentralPubMedCrossRef

76.

Ahmad T, Armuzzi A, Neville M, Bunce M, Ling KL, et al. The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis. Tissue Antigens. 2003;62:527–35.PubMedCrossRef

77.

Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, et al. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology. 1997;112:1845–53.PubMedCrossRef

78.

Ahmad T, Marshall SE, Jewell D. Genetics of inflammatory bowel disease: the role of the HLA complex. World J Gastroenterol. 2006;12:3628–35.PubMed

79.

Chervonsky AV. Influence of microbial environment on autoimmunity. Nat Immunol. 2010;11:28–35.PubMedCrossRef

80.

Birney E. Chromatin and heritability: how epigenetic studies can complement genetic approaches. Trends Genet. 2011;5:172–6.CrossRef

81.

Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol. 2013;2:142–7.CrossRef

82.

Ventham NT, Kennedy NA, Nimmo ER, Satsangi J. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013;145:293–308.PubMedCentralPubMedCrossRef

Titel: Characteristics of Japanese inflammatory bowel disease susceptibility loci
verfasst von: Yoshiaki Arimura
Hiroyuki Isshiki
Kei Onodera
Kanna Nagaishi
Kentaro Yamashita
Tomoko Sonoda
Takayuki Matsumoto
Atsushi Takahashi
Masakazu Takazoe
Keiko Yamazaki
Michiaki Kubo
Mineko Fujimiya
Kohzoh Imai
Yasuhisa Shinomura
Publikationsdatum: 01.08.2014
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 8/2014
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-013-0866-2

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Characteristics of Japanese inflammatory bowel disease susceptibility loci

Abstract

Background

Methods

Results

Conclusions

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Results

Conclusions

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