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参与血清总IgE水平性别差异及过敏性疾病的免疫制动基因CTLA-4(+49)的多态性

Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases.

作者信息

Yang K D, Liu C-A, Chang J-C, Chuang H, Ou C-Y, Hsu T-Y, Wang C-L

机构信息

Departments of Medical Research and Obstetrics, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.

出版信息

Clin Exp Allergy. 2004 Jan;34(1):32-7. doi: 10.1111/j.1365-2222.2004.01776.x.

DOI:10.1111/j.1365-2222.2004.01776.x
PMID:14720259
Abstract

BACKGROUND

A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined.

OBJECTIVE

This study was conducted to investigate whether IL-4 promoter (-590 C/T) and cytotoxic T lymphocyte antigen 4 (CTLA-4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of total IgE levels and allergic diseases in a Chinese population.

METHODS

A total of 1333 participants aged 19-49 years were enrolled in this study. Allergic diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis in conjunction with detectable specific IgE in the blood. Polymorphisms of IL-4 promoter (-590) and CTLA-4 (+49) were determined by restriction fragment length polymorphism.

RESULTS

Males or females with allergic diseases had higher total IgE levels than those without (P=0.000). Females with the A/A genotype in the CTLA-4 (+49) position had significantly higher total IgE levels than those with A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1 vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males with different genotypes in the CTLA-4 (+49) position exhibited no difference in the total IgE levels. Females with allergic rhinitis had a significantly higher frequency of the A/A genotype in the CTLA-4 (+49) polymorphism than those without atopic diseases (P=0.016). In contrast, males with and without allergic disorders exhibited no significant difference in the CTLA-4 (+49) polymorphisms (P>0.05). The IL-4 promoter (-590) polymorphisms, however, had no correlation with the total IgE levels or allergic diseases in either females or males.

CONCLUSION

In females only, the CTLA-4 (+49), but not the IL-4 promoter (-590), polymorphism was significantly associated with elevation of total IgE levels and allergic rhinitis. Here, we have, for the first time, demonstrated a gender-linked genetic relationship with allergic disease.

摘要

背景

多种基因与不同种族人群的过敏性疾病相关。过敏性疾病性别差异的遗传基础尚待确定。

目的

本研究旨在调查白细胞介素4(IL-4)启动子(-590 C/T)和细胞毒性T淋巴细胞抗原4(CTLA-4)(+49 A/G)基因多态性是否与中国人群中总IgE水平及过敏性疾病的性别差异相关。

方法

本研究共纳入1333名年龄在19至49岁之间的参与者。过敏性疾病通过哮喘、鼻炎或特应性皮炎的存在以及血液中可检测到的特异性IgE来识别。IL-4启动子(-590)和CTLA-4(+49)的基因多态性通过限制性片段长度多态性来确定。

结果

患有过敏性疾病的男性或女性的总IgE水平高于未患过敏性疾病者(P = 0.000)。CTLA-4(+49)位点为A/A基因型的女性的总IgE水平显著高于A/G基因型者,而G/G基因型者的IgE水平最低(154.9 vs. 107.1 vs. 79.8 KU/L;平均对数值:1.79 vs. 1.65 vs. 1.54,P < 0.001)。然而,CTLA-4(+49)位点不同基因型的男性在总IgE水平上无差异。患有过敏性鼻炎的女性在CTLA-4(+49)基因多态性中A/A基因型的频率显著高于无特应性疾病者(P = 0.016)。相比之下,患有和未患过敏性疾病的男性在CTLA-4(+49)基因多态性上无显著差异(P > 0.05)。然而,IL-4启动子(-590)基因多态性与女性或男性的总IgE水平及过敏性疾病均无相关性。

结论

仅在女性中,CTLA-4(+49)基因多态性而非IL-4启动子(-590)基因多态性与总IgE水平升高及过敏性鼻炎显著相关。在此,我们首次证明了与过敏性疾病的性别相关遗传关系。

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