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日本成年哮喘患者群体中白细胞介素-13基因多态性与气道高反应性的关联

Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population.

作者信息

Utsumi Yu, Sasaki Nobuhito, Nagashima Hiromi, Suzuki Naomi, Nakamura Yutaka, Yamashita Masahiro, Kobayashi Hitoshi, Yamauchi Kohei

机构信息

Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka 020-8505, Japan.

出版信息

Respir Investig. 2013 Sep;51(3):147-52. doi: 10.1016/j.resinv.2013.02.003. Epub 2013 Apr 13.

Abstract

BACKGROUND

A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics.

METHODS

We recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan).

RESULTS

Genotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different. Spirometric data revealed that % FEV1 and % FEF75 were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration.

CONCLUSION

The SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics.

摘要

背景

白细胞介素-13(IL-13)基因中的单核苷酸多态性(SNP;rs20541)已被确认为哮喘的一个风险因素。该SNP导致成熟IL-13蛋白第110位的精氨酸被谷氨酰胺(Q)取代。我们最近发现,携带IL-13 Q110变体的哮喘患者的第一秒用力呼气容积(FEV1)下降得更快,并且在这些受试者中观察到了进行性气道重塑(Wynn,2003 [1])。然而,IL-13变体对气道高反应性(AHR)的影响仍有待阐明。我们分析了哮喘患者中IL-13基因SNP rs20541与AHR之间的关系。

方法

我们招募了2006年至2011年期间到岩手医科大学医院哮喘门诊就诊的182名哮喘患者。对受试者进行rs20541基因分型。研究了这些受试者的哮喘严重程度、特应性状态、哮喘发病年龄、血清免疫球蛋白E(IgE)浓度、AHR和肺功能。使用连续乙酰甲胆碱吸入法(Astograph;Chest;日本东京)测量AHR。

结果

rs20541基因分型显示有26例患者为A/A基因型、77例为A/G基因型、79例为G/G基因型。三种基因型的最小剂量反应曲线斜率(D min)在A/A基因型中为1.17±0.300,在A/G基因型中为1.99±0.35,在G/G基因型中为2.85±0.39。三种基因型的D min有显著差异。肺功能测定数据显示,三组IL-13基因型之间的FEV1百分比和FEF75百分比有显著差异,而在治疗步骤、特应性状态、屋尘螨致敏或血清IgE浓度方面未观察到显著差异。

结论

IL-13基因中的SNP rs20541与日本成年哮喘患者的AHR相关。

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