Eotaxin启动子上游的核苷酸重复序列与哮喘，血清总IgE及血浆Eotaxin水平相关
2007/08/01
嗜酸粒细胞特异性趋化因子(eotaxin，CCL11 )，为一种很强的嗜酸粒细胞趋化物，是哮喘患者肺部产生的小分子蛋白质。作者目的在于通过病例对照和家系为基础联合研究阐明嗜酸粒细胞特异性趋化因子的多态性在哮喘中的作用。对年龄、性别、种族相匹配的235例哮喘患者、239例健康对照，和来源北或西北印度230个哮喘患者家系的嗜酸粒细胞特异性趋化因子进行基因分型，得到以下多态型：+67G/A, -384A/G和-426C/T以及其启动子10.9 kb上游的核苷酸重复序列 (GAAGGA)(n)。应用ELISA检测血清总IgE (TsIgE)和血浆嗜酸粒细胞特异性趋化因子水平。
研究结果显示在病例对照和家系为基础的研究中+67G/A多态型和哮喘均显著相关 (病例对照，p = 0.009；家系，p = 0.006)，+67G/A多态型的功能和血浆嗜酸粒细胞特异性趋化因子水平显著相关 (p = 0.006)。而且-384C/T和TsIgE(p = 0.016)，以及血浆嗜酸粒细胞特异性趋化因子(p = 0.007)水平显著相关。更为有趣的是首次发现核苷酸重复序列 (GAAGGA)(n)和哮喘 (p = 3x10(-6)), log(10)TsIgE (p = 0.006)，血浆嗜酸粒细胞特异性趋化因子(p = 0.004)高度相关。单倍型G_A_C_8被鉴定为高水平TsIgE和血浆嗜酸粒细胞特异性趋化因子的危险因素。
最后，作者认为该研究为嗜酸粒细胞特异性趋化因子的多态性和哮喘发生的相关性提供了更为有力的证据，其机理为嗜酸粒细胞特异性趋化因子的多态性调节了血浆嗜酸粒细胞特异性趋化因子水平，而且加强了17q21位点与哮喘及相关基因型的细胞因子的表达。
（韩福军 广州医学院第一附属医院 广州呼吸疾病研究所 510120 摘译）
(J Med Genet. 2007 ;44:397-403 )
Batra J, Rajpoot R, Ahluwalia J, Devarapu SK, Sharma SK, Dinda AK, Ghosh B.
A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.
J Med Genet. 2007 Jun;44(6):397-403
BACKGROUND: Eotaxin (CCL11) is a small protein produced in the lungs of patients with asthma, and is a potent chemoattractant for eosinophils.
AIM: To elucidate the role of eotaxin in asthma by an association study of functional and novel eotaxin polymorphisms in case-control and family-based study designs.
METHODS: Eotaxin +67G/A, -384A/G and -426C/T single-nucleotide polymorphisms and a hexanucleotide (GAAGGA)(n) repeat 10.9 kb upstream of the gene were genotyped in a cohort of age, sex and ethnically matched patients with asthma (n = 235) and healthy controls (n = 239), and also in a study population of 230 families with asthma recruited from north/northwest India. Total serum IgE (TsIgE) and plasma eotaxin levels were measured using ELISA.
RESULTS: +67G/A polymorphism was found to be significantly associated with asthma in case-control (p = 0.009) and family-based studies (p = 0.006). Its functional role, as it was correlated with plasma eotaxin levels (p = 0.006), was also demonstrated. Further, -384C/T single-nucleotide polymorphism was found to be significantly associated with log(10) TsIgE (p = 0.016 in case-control and p = 0.018 in families) and eotaxin levels (p = 0.007). Most interestingly, for the first time, a highly significant association of the newly studied (GAAGGA)(n) hexanucleotide repeat with asthma (p = 3x10(-6)), log(10)TsIgE (p = 0.006) and eotaxin levels (p = 0.004) was observed. G_A_C_8 was also identified as an important risk haplotype associated with high TsIgE and plasma eotaxin levels.
CONCLUSIONS: This study provides further evidence that eotaxin polymorphisms are associated with the development of asthma by regulating eotaxin levels and reinforces towards the scanning of other chemokine genes present at 17q21 locus for their association with asthma and related phenotypes.
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