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Association of miR-146a Gene Polymorphism at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C with Susceptibility to Kawasaki Disease in Chinese Children

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Abstract

Objective

To investigate the genetic association of miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with Kawasaki disease (KD) and coronary artery lesions (CAL).

Methods

There were 120 patients with KD and 126 healthy subjects in this study. The genotype of loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected by polymerase chain reaction-sequence-based typing.

Results

For miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there were no significant difference of genotype frequencies and allele frequencies between KD group and healthy control group, or between the IVIG-resistant group and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL) group, the genotype frequencies of GG were higher than that in KD without coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR-146a gene (χ2 = 6.660, P = 0.036), patients with KD carried genotype of GG were at 3.636 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280–10.262). While there was no significant difference of allele frequency of G and C between KD-CAL group and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene (χ2 = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 4.745, P = 0.035, OR = 2.422, 95%CI = 1.073–5.465), while there was no significant difference of genotype frequency of AA, AG, and GG types between KD-CAL group and KD-WO group (P > 0.05). There was no significant difference of genotype frequencies of TT, TC, and CC types and allele frequencies of T and C types between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR-146a gene (P > 0.05).

Conclusions

The significant association has been found between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329 A/G were risk factors for getting coronary artery lesions.

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References

  1. Kawasaki T (1967) Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 16:178–222

    CAS  PubMed  Google Scholar 

  2. Llave C, Xie Z, Kasschau KD, Carrington JC (2002) Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297:2053–2056

    Article  CAS  PubMed  Google Scholar 

  3. Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, de Vries N, Tak PP, Tsao BP, Shen N (2011) A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet 7:e1002128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Singh S, Sharma A, Jiao F (2016) Kawasaki disease: issues in diagnosis and treatment-a developing country perspective. Indian J Pediatr 83:140–145

    Article  PubMed  Google Scholar 

  5. Bayers S, Shulman ST, Paller AS (2013) Kawasaki disease: part I. Diagnosis, clinical features, and pathogenesis. J Am Acad Dermatol 69:501.e1–501.e11

    Article  Google Scholar 

  6. Singh S, Vignesh P, Burgner D (2015) The epidemiology of Kawasaki disease: a global update. Arch Dis Child 100:1084–1088

    Article  PubMed  Google Scholar 

  7. Makino N, Nakamura Y, Yashiro M, Ae R, Tsuboi S, Aoyama Y, Kojo T, Uehara R, Kotani K, Yanagawa H (2015) Descriptive epidemiology of Kawasaki disease in Japan, 2011–2012: from the results of the 22nd nationwide survey. J Epidemiol 25:239–245

    Article  PubMed  Google Scholar 

  8. Kim GB, Han JW, Park YW, Song MS, Hong YM, Cha SH, Kim DS, Park S (2014) Epidemiologic features of Kawasaki disease in South Korea: data from nationwide survey,2009–2011. Pediatr Infect Dis J 33:24–27

    Article  PubMed  Google Scholar 

  9. Lin MC, Lai MS, Jan SL, Fu YC (2015) Epidemiologic features of Kawasaki disease in acute stages in Taiwan,1997–2010:Effect of different case definitions in claims data analysis. J Chin Med Assoc 78:121–126

    Article  PubMed  Google Scholar 

  10. Onouchi Y (2012) Genetics of Kawasaki disease: what we know and don’t know. Circ J 76:1581–1586

    Article  CAS  PubMed  Google Scholar 

  11. Kuo HC, Hsu YW, Lo MH, Huang YH, Chien SC, Chang WC (2014) Single-nucleotide polymorphism rs7251246 in ITPKC is associated with susceptibility and coronary artery lesions in Kawasaki disease. PLoS ONE 9:e91118

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lin YJ, Chang JS, Liu X, Hung CH, Lin TH, Huang SM, Jeang KT, Chen CY, Liao CC, Lin CW, Lai CH, Tien N, Lan YC, Ho MW, Chien WK, Chen JH, Huang YC, Tsang H, Wu JY, Chen CH, Chang LC, Tsai FJ (2013) Association between GRIN3A gene polymorphism in Kawasaki disease and coronary artery aneurysms in Taiwanese children. PLoS ONE 8:e81384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Duan J, Lou J, Zhang Q, Ke J, Qi Y, Shen N, Zhu B, Zhong R, Wang Z, Liu L, Wu J, Wang W, Gong F, Miao X (2014) A genetic variant rs1801274 in FCGR2A as a potential risk marker for Kawasaki disease: a case-control study and meta-analysis. PLoS ONE 9:e103329

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li Z, Han D, Jiang J, Chen J, Tian L, Yang Z(2017). Association of PECAM-1 gene polymorphisms with Kawasaki disease in Chinese children. Dis Mark 2017:2960502

    Google Scholar 

  15. Lu Y, Liu R, Zha L, Yuan S, Tian L, Chen J, Huang L, Yang Z(2018). Association of thrombomodulin Gene C1418T polymorphism with susceptibility to Kawasaki disease in Chinese children. Dis Mark 2018:1064380

    Google Scholar 

  16. Guo M, Mao XB, Ji QW, Lang M, Li S, Peng Y, Zhou W, Xiong B, Zeng Q (2010) MiR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome. Immunol Cell Biol 88:555–555

    Article  CAS  PubMed  Google Scholar 

  17. Kalyani A, Sonawane PJ, Khan AA, Subramanian L, Ehret GB, Mullasari AS, Mahapatra NR (2015) Post-transcriptional regulation of renalase gene by miR-29 and miR-146 MicroRNAs: implications for cardiometabolic disorders. J Mol Biol 427:2629–2646

    Article  CAS  PubMed  Google Scholar 

  18. Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, Ishii M, Harada K(2005). Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition) Pediatr Int 47:232–234

    Article  PubMed  Google Scholar 

  19. JCS Joint Working Group (2005) Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2013). Digest version. Pediatr Int 47:711–732

    Article  Google Scholar 

  20. Kamali K, Korjan ES, Eftekhar E, Malekzadeh K, Soufi FG (2016) The role of miR-146a on NF-κB expression level in human umbilical vein endothelial cells under hyperglycemic condition. Bratisl Lek Listy 117:376–380

    CAS  PubMed  Google Scholar 

  21. Zhang Y, Wang F, Lan Y, Zhou D, Ren X, Zhao L, Zhang Q (2015) Roles of microRNA-146a and microRNA-181b in regulating the secretion of tumor necrosis factor-α and interleukin-1β in silicon dioxide-induced NR8383 rat macrophages. Mol Med Rep 12:5587–5593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappa B-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486

    Article  CAS  PubMed  Google Scholar 

  23. So AY, Zhao ZY, Baltimore D (2013) The Yin and Yang of microRNAs: leukemia and immunity. Immunol Rev 253:129–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen JQ, Papp G, Póliska S, Szabó K, Tarr T, Bálint BL, Szodoray P, Zeher M (2017) MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren’s syndrome. PLoS ONE 12:e0174585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nakasha T, Shibuya H, Nagata Y, Niimoto T, Ochi M (2011) The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis. Arthritis Rheum 63:1582–1590

    Article  CAS  Google Scholar 

  26. Niu Z, Wang J, Zou H, Yang C, Huang W, Jin L (2015) Common MIR146A polymorphisms in Chinese ankylosing spondylitis subjects and controls. PLoS ONE 10:e0137770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tseng WN, Lo MH, Guo MM, Hsieh KS, Chang WC, Kuo HC (2014) IL-31 associated with coronary artery lesion formation in Kawasaki disease. PLoS ONE 9:e105–e195

    Google Scholar 

  28. Jiang J, Cai Y, Li Z, Huang L, Chen J, Tian L, Wu Z, Li X, Chen Z, Chen C, Yang Z (2017) Screening of differentially expressed genes associated with Kawasaki disease by microarray analysis. Exp Ther Med 14:3159–3164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lee Y, Schulte DJ, Shimada K, Chen S, Crother TR, Chiba N, Fishbein MC, Lehman TJ, Arditi M (2012) Interleukin-1β is crucial for the induction of coronary artery inflammation in a mouse model of Kawasaki disease. Circulation 125:1542–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee Y, Wakita D, Dagvadorj J, Shimada K, Chen S, Huang G, Lehman TJ, Fishbein MC, Hoffman HM, Crother TR, Arditi M (2015) IL-1 signaling is critically required in stromal cells in Kawasaki disease vasculitis mouse model: role of both IL-1α and IL-1β. Arterioscler Thromb Vasc Biol 35:2605–2616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sánchez-Manubens J, Gelman A, Franch N, Teodoro S, Palacios JR, Rudi N, Rivera J, Antón J. (2017). A child with resistant Kawasaki disease successfully treated with anakinra: a case report. BMC Pediatr 17:102

    Article  PubMed  PubMed Central  Google Scholar 

  32. Liu Q, Wang W, Yang XF, Zhao D, Li F, Wang H (2016) MicroRNA-146a inhibits cell migration and invasion by targeting RhoA in breast cancer. Oncol Rep 36:189–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li YL, Wang J, Zhang CY, Shen YQ, Wang HM, Ding L, Gu YC, Lou JT, Zhao XT, Ma ZL, Jin YX(2016). MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2. Oncotarget 7:59287

    PubMed  PubMed Central  Google Scholar 

  34. Dunand-Sauthier I, Santiago-Raber ML, Capponi L, Vejnar CE, Schaad O, Irla M, Seguín-Estévez Q, Descombes P, Zdobnov EM, Acha-Orbea H, Reith W (2011) Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function. Blood 117:4490–4500

    Article  CAS  PubMed  Google Scholar 

  35. Zhang W, Shao M, He X, Wang B, Li Y, Guo X (2018) Overexpression of microRNA-146 protects against oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis by inhibiting the NF-κB/TNF-α signaling pathway. Mol Med Rep 17:1913–1918

    CAS  PubMed  Google Scholar 

  36. Bastami M, Ghaderian SM, Omrani MD, Mirfakhraie R, Vakili H, Parsa SA, Nariman-Saleh-Fam Z, Masotti A (2016) MiRNA-related polymorphisms in miR-146a and TCF21 are associated with increased susceptibility to coronary artery disease in an iranian population. Genet Test Mol Biomark 20:241–248

    Article  CAS  Google Scholar 

  37. Huang S, Lv Z, Deng Q, Yang B, Feng J, Wu T, Zhang X, Cheng J (2015) A genetic variant in Pre-miR-146a (rs2910164 C > G) is associated with the decreased risk of acute coronary syndrome in a Chinese population. Tohoku J Exp Med 237:227–233

    Article  CAS  Google Scholar 

  38. Qu JY, Xi J, Zhang YH, Zhang CN, Song L, Song Y, Hui RT, Chen JZ (2016) Association of the MicroRNA-146a SNP rs2910164 with ischemic stroke incidence and prognosis in a Chinese population. Int J Mol Sci 17:660

    Article  CAS  PubMed Central  Google Scholar 

  39. Kim YR, Hong SH (2016) Associations of MicroRNA polymorphisms (miR-146a, miR-196a2, and miR-499) with the risk of hypertension in the Korean population. Genet Test Mol Biomark 20:420–426

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the New Xiangya Talent Project of the Third Xiangya Hospital of the Central South University (Grant No. JY20150312). This work was also supported by grants from the Science and Technology Projects of Changsha City (No. kq1602042).

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Authors and Affiliations

  1. Department of Pediatrics, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China

    Luting Zha, Shentang Li, Xin Liu, Zhuoying Li, Jie Jiang & Zuocheng Yang

  2. Central Laboratory, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China

    Lihua Huang

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  1. Luting Zha
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Zha, L., Li, S., Liu, X. et al. Association of miR-146a Gene Polymorphism at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C with Susceptibility to Kawasaki Disease in Chinese Children. Pediatr Cardiol 40, 504–512 (2019). https://doi.org/10.1007/s00246-018-2002-9

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  • DOI: https://doi.org/10.1007/s00246-018-2002-9

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