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中国儿童中,miR-146a基因rs2910164 G/C、rs57095329 A/G和rs6864584 T/C位点多态性与川崎病易感性的关联。

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.

作者信息

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

机构信息

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

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

出版信息

Pediatr Cardiol. 2019 Mar;40(3):504-512. doi: 10.1007/s00246-018-2002-9. Epub 2018 Oct 5.

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 (χ = 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 (χ = 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 (χ = 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 (χ = 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.

摘要

目的

探讨川崎病(KD)及冠状动脉病变(CAL)患者中miR-146a基因rs2910164 G/C、rs57095329 A/G和rs6864584 T/C位点的基因多态性。

方法

本研究纳入120例KD患者和126例健康对照者。采用聚合酶链反应-序列分型法检测miR-146a基因rs2910164 G/C、rs57095329 A/G和rs6864584 T/C位点的基因型。

结果

对于miR-146a基因rs2910164 G/C、rs57095329 A/G和rs6864584 T/C位点的多态性,KD组与健康对照组之间,以及IVIG抵抗组与IVIG敏感组之间的基因型频率和等位基因频率均无显著差异(P>0.05)。在有冠状动脉病变的KD(KD-CAL)组中,miR-146a基因rs2910164 G/C多态性位点的GG基因型频率高于无冠状动脉病变的KD(KD-WO)组(χ=6.660,P=0.036),携带GG基因型的KD患者发生冠状动脉病变的风险是非携带者的3.636倍(χ=6.455,P=0.018,OR=3.636,95%CI=1.280-10.262)。而KD-CAL组与KD-WO组之间G和C等位基因频率无显著差异(P>0.05)。在KD-CAL组中,miR-146a基因rs57095329 A/G多态性位点的A等位基因频率高于KD-WO组(χ=4.745,P=0.035),携带A等位基因的患者发生冠状动脉病变的风险是非携带者的2.422倍(χ=4.745,P=0.035,OR=2.422,95%CI=1.073-5.465),而KD-CAL组与KD-WO组之间AA、AG和GG基因型频率无显著差异(P>0.05)。在miR-146a基因rs6864584 T/C多态性位点,KD-CAL组与KD-WO组之间TT、TC和CC基因型频率以及T和C等位基因频率均无显著差异(P>0.05)。

结论

已发现miR-146a基因位点rs2910164 G/C和rs57095329 A/G的基因型和等位基因频率与冠状动脉病变存在显著关联,rs2910164 G/C的GG基因型和rs57095329 A/G的A等位基因是发生冠状动脉病变的危险因素。

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