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细胞因子遗传多态性与台湾儿童川崎病易感性的关系。

Cytokine genetic polymorphisms and susceptibility to Kawasaki disease in Taiwanese children.

机构信息

Department of Pediatrics, Kaohsiung Veterans General Hospital, National Yang-Ming University, Taiwan.

出版信息

Circ J. 2010 Nov;74(12):2726-33. doi: 10.1253/circj.cj-10-0542. Epub 2010 Oct 30.

Abstract

BACKGROUND

The relationship between cytokine gene polymorphisms and susceptibility to Kawasaki diseases (KD) is still controversial, so the aim of the present study was to investigate the association of 14 various polymorphisms of 9 cytokine genes (interleukin (IL)-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-A and transforming growth factor-B) with KD risk.

METHODS AND RESULTS

A total of 211 KD children and 221 adult controls were recruited. All controls were frequency matched to KD patients on sex and ethnicity. PCR and TaqMan assays were used for genotyping. There were no significant differences between KD children and adult controls in the genotype or allelic type frequencies of the 14 polymorphisms. No significant associations were found between haplotypes, constructed by IL-1B, IL-4, IL-8, and IL-10 cytokine genes, and risk of KD. Additionally, a linear trend was observed when these single nucleotide polymorphisms were combined, as evidenced by an increasing risk of KD as the number of at-risk genotypes increased (P(linear trend)=0.002). In the stratification analysis of age and sex, there was a linear trend of KD risk as the number of at-risk genotypes increased among those aged >12 months (P=0.014) or female (P=0.001), respectively.

CONCLUSIONS

No associations between individual cytokine genetic polymorphisms and susceptibility of KD were observed, but a gene-dosage effect on the risk of KD was found, especially for older or female subjects.

摘要

背景

细胞因子基因多态性与川崎病(KD)易感性之间的关系仍存在争议,因此本研究旨在探讨 9 种细胞因子基因(白细胞介素(IL)-1A、IL-1B、IL-1RN、IL-4、IL-6、IL-8、IL-10、肿瘤坏死因子-A 和转化生长因子-B)的 14 种不同多态性与 KD 风险的相关性。

方法和结果

共纳入 211 例 KD 患儿和 221 例成人对照。所有对照均按照性别和种族与 KD 患者进行频数匹配。采用 PCR 和 TaqMan 法进行基因分型。14 种多态性的基因型或等位基因频率在 KD 患儿和成人对照组之间无显著差异。未发现 IL-1B、IL-4、IL-8 和 IL-10 细胞因子基因构建的单倍型与 KD 风险之间存在显著相关性。此外,当这些单核苷酸多态性组合时,观察到线性趋势,即随着风险基因型数量的增加,KD 的风险呈增加趋势(P(线性趋势)=0.002)。在年龄和性别分层分析中,对于年龄>12 个月(P=0.014)或女性(P=0.001),随着风险基因型数量的增加,KD 风险呈线性趋势。

结论

未观察到单个细胞因子遗传多态性与 KD 易感性之间存在相关性,但发现基因剂量效应对 KD 风险有影响,尤其是对于年龄较大或女性患者。

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