目的 探讨成纤维细胞生长因子23(FGF23)基因内含子1 中c.212-37insC(rs3832879)多态性与川崎病(KD)及冠状动脉损伤(CAL)的相关性。方法 40 例KD 患儿纳入该研究,其中16 例并发CAL;26 例年龄匹配的健康儿童作为对照。应用聚合酶链反应、基因测序技术对研究对象FGF23 c.212-37insC(rs3832879)多态性进行研究。结果 40 例KD 患儿中,14 例(35%)患儿具有c.212-37insC(rs3832879)多态性,26 例对照组儿童中6 例(23%)具有此位点多态性,两组间比较该位点基因型分布差异无统计学意义。16 例伴CAL 的患儿中9 例(56%)具有c.212-37insC(rs3832879)多态性,24 例未并发CAL 患儿中5 例(21%)具有此位点多态性,伴CAL 的患儿与不伴CAL 患儿两亚组间比较该位点基因型分布差异有统计学意义(P=0.02,OR=4.89,95%CI:1.21~19.71)。结论 基因FGF23 c.212-37insC(rs3832879)多态性可能与儿童KD 的发生无相关性,但与KD 患儿CAL 的发生相关。
Abstract
Objective To study the distribution of polymorphism of c.212-37insC (rs3832879) in intron 1 of fibroblast growth factor 23 (FGF23) gene and its association with Kawasaki disease (KD) and coronary artery lesions (CAL). Methods Forty children with KD were enrolled in this study, among whom 16 children had concurrent CAL. Twenty-six age-matched healthy children were enrolled as controls. PCR and gene sequencing were applied to explore the distribution of polymorphism of c.212-37insC (rs3832879) in FGF23 gene in KD patients and controls. Results Among 40 children with KD, 14 (35%) carried the polymorphism of c.212-37insC (rs3832879) in FGF23 gene;among 26 controls, 6 (23%) carried such polymorphism. There was no significant difference in genotype distribution at this locus between the two groups (P=0.30). Among 16 children with CAL, 9 (56%) carried the polymorphism at this locus;among 24 children without CAL, 5 (21%) carried such polymorphism. As for the comparison of two subgroups with and without CAL, the difference in genotype distribution at this locus had statistical significance (P=0.02, OR=4.89, 95%CI:1.21-19.71). Conclusions The polymorphism of c.212-37insC (rs3832879) in FGF23 gene may not be associated with the pathogenesis of childhood KD, but it may be associated with the development of CAL in children with KD.
关键词
川崎病 /
成纤维细胞生长因子23 /
单核苷酸多态性 /
冠状动脉损伤 /
儿童
Key words
Kawasaki disease /
Fibroblast growth factor 23 /
Single-nucleotide polymorphism /
Coronary artery lesion /
Child
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参考文献
[1] Eleftheriou D, Levin M, Shingadia D, et al. Management of Kawasaki disease[J]. Arch Dis Child, 2014, 99(1):74-83.
[2] Matsushita K, Tamura T, Nishiga M, et al. Acute myocardial infarction and 30-year coronary aneurysm follow-up by serial angiography in a young adult with Kawasaki disease[J]. Cardiovasc Interv Ther, 2015, 30(2):142-146.
[3] Cho HJ, Yang SI, Kim KH, et al. Cardiovascular risk factors of early atherosclerosis in school-aged children after Kawasaki disease[J]. Korean J Pediatr, 2014, 57(5):217-221.
[4] Giacchi V, Sciacca P, Stella I, et al. Assessment of coronary artery intimal thickening in patients with a previous diagnosis of Kawasaki disease by using high resolution transthoracic echocardiography:our experience[J]. BMC Cardiovasc Disord, 2014, 14(1):106-112.
[5] 陈婧, 马彬, 林丽星, 等. 不同剂量丙种球蛋白治疗川崎病的疗效的Meta 分析[J]. 中国当代儿科杂志, 2011, 13(8):638-643.
[6] Isakova T, Houston J, Santacruz L, et al. Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure[J]. Pediatr Nephrol, 2013. 28(10):2035-2042.
[7] Masi L, Franceschelli F, Leoncini G, et al. Can fibroblast growth factor (FGF)-23 circulating levels suggest coronary artery abnormalities in children with Kawasaki disease?[J]. Clin Exp Rheumatol, 2013, 31(1):149-153.
[8] Falcini F, Rigante D, Masi L, et al. Fibroblast growth factor 23 (FGF23) gene polymorphism in children with Kawasaki syndrome (KS) and susceptibility to cardiac abnormalities[J]. Ital J Pediatr, 2013, 39(1):69-73.
[9] Guidelines for diagnosis and management of cardiovascular sequelae in kawasaki disease (JCS 2013)[J]. Circ J, 2014, 78(10):2521-2562.
[10] Ohta H, Itoh N. Roles of FGFs as adipokines in adipose tissue development, remodeling, and metabolism[J]. Front Endocrinol (Lausanne), 2014, 5(14):18-22.
[11] Isakova T, Xie H, Yang W, et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease[J]. JAMA, 2011, 305(23):2432-2439.
[12] Zoccali C, Yilmaz MI, Mallamaci F. FGF23:a mature renal and cardiovascular risk factor?[J]. Blood Purif, 2013, 36(1):52-57.
[13] Kendrick J, Cheung AK, Kaufman JS, et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis[J]. J Am Soc Nephrol, 2011, 22(10):1913-1922.
[14] Shibata K, Fujita S, Morita H, et al. Association between circulating fibroblast growth factor 23, alpha-Klotho, and the left ventricular ejection fraction and left ventricular mass in cardiology inpatients[J]. PLoS One, 2013, 8(9):e73184.
[15] Seiler S, Cremers B, Rebling NM, et al. The phosphatonin fibroblast growth factor 23 links calcium-phosphate metabolism with left-ventricular dysfunction and atrial fibrillation[J]. Eur Heart J, 2011, 32(21):2688-2696.
[16] Poelzl G, Trenkler C, Kliebhan J, et al. FGF23 is associated with disease severity and prognosis in chronic heart failure[J]. Eur J Clin Invest, 2014,44(12):1150-1158.
[17] Brandenburg VM, Kleber ME, Vervloet MG, et al. Fibroblast growth factor 23 (FGF23) and mortality:The Ludwigshafen Risk and Cardiovascular Health Study[J]. Atherosclerosis, 2014, 237(1):53-59.
[18] Touchberry CD, Green TM, Tchikrizov V, et al. FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy[J]. Am J Physiol Endocrinol Metab, 2013, 304(8):E863-873.
[19] Kovesdy CP, Quarles LD. Fibroblast growth factor-23:what we know, what we don't know, and what we need to know[J]. Nephrol Dial Transplant, 2013, 28(9):2228-2236.
[20] Bacchetta J, Sea JL, Chun RF, et al. Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes[J]. J Bone Miner Res, 2013, 28(1):46-55.
[21] Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy[J]. J Clin Invest, 2011, 121(11):4393-4408.
[22] Itoh N, Ohta H. Pathophysiological roles of FGF signaling in the heart[J]. Front Physiol, 2013, 4(10):247-251.
[23] Wang W, Lou J, Zhong R, et al. The roles of Ca2+/NFAT signaling genes in Kawasaki disease:single-and multiple-risk genetic variants[J]. Sci Rep, 2014, 4(8):5208-5215.
[24] Onouchi Y, Suzuki Y, Suzuki H, et al. ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease[J]. Pharmacogenomics J, 2013, 13(1):52-59.
[25] Kuo HC, Hsu YW, Wu CM, et al. A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease[J]. PLoS One, 2013, 8(7):e69685.
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