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A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.

ABSTRACT: 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.

SUBMITTER: Batra J

PROVIDER: S-EPMC2740889 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.

Batra Jyotsna J Rajpoot Reenu R Ahluwalia Jasmine J Devarapu Satish K SK Sharma Surendra K SK Dinda Amit K AK Ghosh Balaram B

Journal of medical genetics 20070112 6

<h4>Background</h4>Eotaxin (CCL11) is a small protein produced in the lungs of patients with asthma, and is a potent chemoattractant for eosinophils.<h4>Aim</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 17220216

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Project description:BackgroundOmalizumab (OMA) is an effective anti-immunoglobulin E (IgE) treatment for moderate-to-severe asthma. However, predicting an individual's response is difficult. Monitoring change of total serum IgE may be useful for predicting the response to OMA. The purpose of this study was to determine if measuring the change in total IgE level could predict the response to OMA in patients with moderate-to-severe asthma.MethodsThis study included 25 patients (11 females and 14 males; mean age =46.1 years; mean pre-bronchodilator FEV1% =67.8%) with moderate-to-severe asthma. All patients were treated with OMA, and total IgE serum concentrations were measured at baseline before treatment (median baseline total serum IgE =210 IU/mL) and at 4 weeks after beginning treatment. Patients were divided into responders (i.e., excellent or good response) and non-responders (i.e., moderate or poor response) using the global treatment effectiveness (GETE) response method after 16 weeks of treatment. The characteristics of responders and non-responders were compared, and receiver operating characteristic (ROC) curve analysis was used to determine the ability of change in IgE level to predict treatment response.ResultsThere were 20 responders (80%) and 5 non-responders (20%), and responders demonstrated better improvements of asthma control test (ACT) and asthma control questionnaire (ACQ) scores, and reduction of oral corticosteroid use as compared with non-responders. Twenty-one patients had a total serum IgE 4-week-to-baseline ratio ≥2, and 20 of the patients responded to OMA. The area under the ROC curve (AUC) for baseline IgE level for predicting treatment response was 0.53 (95% CI: 0.18-0.88), and that of the week 4 IgE level was 0.69 (95% CI: 0.42-0.96). Using a cutoff value of 2, the 4-week: baseline IgE ratio achieved the highest AUC of 0.87 (95% CI: 0.64-1), with a sensitivity and specificity of 100% and 80%, respectively, for predicting treatment response.ConclusionsA total week 4 serum IgE level:baseline level ratio ≥2 can predict the response to OMA in patients with moderate-to-severe asthma after 16 weeks of treatment with high likelihood. Monitoring changes of total IgE level in asthma patients treated OMA may be useful for predicting clinical response.

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Dataset Information

A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.

Publications

A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.

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