The Relationship Between Vitamin D And Bronchial Asthma Susceptibility And Relevant Traits In A Chinese Han Population

Backgroud:Asthma has been recognized as a typical complex disease with a high number of factors modulating the expression of asthma-related phenotypes or outcomes. It has been suggested that decreasing sun exposure may in part play a potential role in asthma etiology. Vitamin D has been thought to mediate the observed association between sun exposure and asthma. In recent years the Vitamin D pathway has emerged as a new potential component of asthma and allergy susceptibility.The polymorphisms of main genes involved in the metabolic pathway of vitamin D were associated with asthma susceptibility. The main mechanisms involved in interactions of vitamin D and enviornmental risk factors on immune imbalance, and influence of vitamin D on lung maturation. Therefore, better understanding the roles of vitamin D and related products in asthma pathogenesis in which they mediate may be helpful in reversing the recently rising prevalence of asthma, and provides a potential way to asthma prevention and treatment. Objective:1.To investigate serum vitamin D status in Chinese adults with newly diagnosed asthma.2. To examine whether vitamin D status was associated with lung function and total serum IgE.3. In order to test whether main genes involved in the metabolic pathway of vitamin D, including VDR, CYP2R1 and GC genes were associated with asthma in a Han Chinese Population. Methods:1. The diagnosis of asthma, recuitment of participants, collection of blood samples and measurement of lung function of participants, including the forced expiratory volume in 1 s (FEVt), FEV1% predicted, and FEV1/forced vital capacity (FVC), and serum total IgE concentration.2. Seperation of serum of blood samples and extraction of genomic DNA.3. We conducted a cross-sectional study including 435 Chinese patients aged>18 years with newly diagnosed asthma. Vitamin D status was assessed by measuring serum 25-(OH)-VD concentrations with ELISA method. Then we analyzed the association between 25-(OH)-VD concentration and lung function, as well as serum total IgE concentration.4. In a Han ethnicity Chinese case-control cohort consisting of 467 asthma patients and 288 unrelated disease free controls recruited from the Northern region of China, we investigated polymorphisms of three main genes involved in the metabolic pathway of vitamin D, including VDR, CYP2R1 and GC gene. We sequenced all 8 coding exons of VDR gene and all 5 exons of CYP2R1 gene to detect variations. We also genotyped two common polymorphisms (rs4588 and rs7041) of GC gene by a PCR-RFLP method. Then we analyzed the association between the polymorphisms and asthma susceptibility and asthma relevant traits.Results:1. In this study, vitamin D deficiency was highly prevalent in in Chinese adults with asthma, Of the 435 participants,88.9%(387 participants) of the subjects having serum 25-(OH)-VD<50 nmol/1.2. Serum 25-(OH)-VD concentration was positively correlated with FEV1% predicted(P= 0.02, r=0.12). After adjusting for age, sex, body mass index, smoking, month of blood collection, and symptom duration, we found significant positive associations between serum 25-(OH)-VD concentrations and FEV1(in liters), FEV1% predicted, and FEV1/FV(P for trend <0.05 for all). The adjusted odds ratios for the highest versus the lowest 25-(OH)-VD concentration quartile were 0.50 (95% CI 0.26-0.96;P=0.007) for FEV,<75% predicted and 0.44 (95% CI 0.20-0.95; P=0.007) for FEV1/FVC<0.75. There was no significant association between 25-(OH)-VD concentrations and serum total IgE or the peripheral blood eosinophil count.3.We sequenced all coding exons of VDR and CYP2R1 genes and identified two already known SNPs--VDR/SNP (rs2228570; Fok I) and CYP2R1/SNP (rs12794714). Then we observed no associations between the SNPs and asthma susceptibility and asthma relevant traits, including blood Eosinphil counts, log-transformed serum IgE or lung function measures, even after stratification by sex.4. Two common SNPs(rs4588 and rs7041) at codons 416 and 420 of exon 11 of the GC gene give rise to the three genotypes-Gcl/1, Gc1/2 and Gc2/2. Compared with Gc1/1 genotype, Gc2/2 genotype was strongly associated with the risk of asthma (OR=13.13,95% CI 2.42-7.13,P=0.001). However, we did not observe a significant relationship between the GC polymorphisms and blood Eosinphil counts, log-transformed serum IgE or lung function measures.as well as serum 25-(OH)-VD concentrations. Conclusion:1. Vitamin D deficiency was highly prevalent in Chinese asthma patients, and vitamin D status was positively associated with lung function.2. The results provide supporting evidence for association between GC variants and asthma susceptibility in the Chinese Han population.3. The exonic variants of VDR and CYP2R1 genes were not associated with asthma susceptibility in the Chinese Han population.