Association Study Of Surfactant Protein A And Surfactant Protein D Polymorphisms With Allergic Rhinitis In A Chinese Han Population

Pulmonary surfactant protein A (SP-A) and pulmonary surfactant protein D (SP-D) in the respiratory tract play an important role in host defense. In this study,we speculated that SP-A and SP-D gene locus specific nucleotide variations or immunomodulatory changes may affect different individuals of susceptibility to allergic rhinitis.There are three parts in this study. The first part is mainly about the expressions of SP-A and SP-D in the upper respiratory tract inflammation.Eleven cases of allergic rhinitis, fifteen cases of polyp and seven cases of normal middle turbinate were studied with immunohistochemistry and immunofluorescence method to detect the expression of SP-A and SP-D.The expression of SP-A and SP-D in allergic rhinitis and polyp were dramatically higher than in controls(P<0.05), the expression of SP-A and SP-D between allergic rhinitis and polyp was no remarkable difference(P>0.05).The result demonstrated that SP-A and SP-D were positivly correlated with eosinophils within the basement membrane of epithelium(R=0.81,0.55).In the result of immunofluorescence, there was significantly higher expression SP-A and SP-D in nasal mucosa of allergic rhinitis and nasal polyp than that in control group(P<0.05).SP-A and SP-D likely play key roles in the inflammatory reaction process of allergic rhinitis and polyp. Its secretion in the upper airway indicates that future studies may allow manipulation of this protein and development of novel treatments for sinonasal pathology.The development of allergic rhinitis is considered to be determined by the interaction between genetic and environmental factors. Surfactant protein A (SP-A), a member of the collectin family of proteins, plays an important role in immune regulation. The purpose of this study was to investigate the association between SP-A polymorphisms and allergic rhinitis.We conducted a case-control association study on a Chinese Han population, comprising 216 adult individuals with AR and 84 healthy controls. A total of 9 single-nucleotide polymorphisms (SNPs) were mapped to the SFTPA gene were genotyped using PCR-based molecular identification methods.The frequency of A allele at amino acid 223 in the patient group was significantly higher than that in the control group after correcting for multiple testing (P=0.006). The 1A2 allele haplotype in SFTPA2 are associated with decreased risk for allergic rhinitis, after applying Bonferroni corrections (P=0.003). However, genetic variants of the SFTPA1 genes were not found to be associated with AR. In addition, no significant associations were established between any of the 9 SFTPA gene polymorphisms and the skin-prick test responses (P>0.05). Further, no association was established between the 9 SNP loci and the levels of total serum immunoglobulin E (IgE) (P>0.05).These results indicate that the gene polymorphism at the residue 223 in the carbohydrate recognition domain of SFTPA2 may be a genetic marker for the development of AR in the adult Chinese Han population.The third part mainly about investigate the association between SP-D polymorphisms and allergic rhinitis phenotypes in Chinese. SP-D genotype were detected in 216 allergic rhinitis patients and 84 health control by the method of pyrosequencing.Total IgE and specific IgE of Der p/f, mold with different genotype of the three loci were compared.In comparison to the controls, the patient group showed no significant difference in terms of either allele or genotype frequency, in either the Ala160Thr(rs2243639) or Ser270Thr(rs3088308) SNP (P>0.05). The genotype and allele frequencies of Met11Thr(rs721917) in allergic rhinitis patients were significantly different from those in the control group (P<0.05). Importantly, significantly more allergic patients had the C allele compared to the control subjects (P=0.006).Among patients who were allergic rhinitis,there were no significant association between any of these three SFTPD gene polymorphisms and serum-specific IgE(P>0.05). Pyrosequencing is an ideal technique that could improve the efficiency of SNP analysis for clinical genetic studies in a large sample population.Single nucleotide polymorphism of SP-D is associated with the allergic rhinitis susceptibility in the southern part of China,it may be an important candidate gene for allergic rhinitis.