Vitamin D binding protein variants associate with asthma susceptibility in the Chinese han population

We sequenced all 8 exons of VDR and all 5 exons of CYP2R1 in a Chinese case-control cohort of asthma consisting of 467 cases and 288 unrelated healthy controls. Two mutations were identified in these regions. These variants were specified as rs2228570 in exon 2 of VDR and rs12794714 in exon 1 of CYP2R1. We also genotyped two common polymorphisms in GC gene (rs4588 and rs7041) by a PCR-restriction fragment length polymorphism (RFLP) method. We analyzed the association between these 4 polymorphisms and asthma susceptibility and asthma-related traits.Polymorphic markers in VDR and CYP2R1 were not associated with asthma in the Chinese Han cohort. Importantly, variants in GC gene, which give rise to the two most common electrophoretic isoforms of the vitamin D binding protein, were associated with asthma susceptibility. Compared with isoform Gc1, Gc2 was significantly associated with the risk of asthma (OR = 1.35, 95% CI = 1.01-1.78 p = 0.006).The results provide supporting evidence for association between GC variants and asthma susceptibility in the Chinese Han population.Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction and airway hyper-reactivity. The disease exhibits complex patterns of transmission, and has an estimated heritability of 36 - 79% [1]. To date, a plethora of genes and variants have been implicated in the pathogenesis and progression of asthma [2,3]. However, relatively few of these genes and variants have been successfully replicated.In recent years the vitamin D pathway has emerged as a new potential component of asthma and allergy susceptibility. The majority of this evidence has been derived from epidemiological surveys. Deficiency of vitamin D has been found to increase the risk of asthma or asthma exacerbation [4-8]; higher maternal vitamin D intake during pregnancy has been associated with a reduced risk of wheezing illnesses in young children [9-11]; and circulating 25-hydroxyvitamin D (25OHD