Abstract
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) mapped to the SP-A 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 was 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.
Similar content being viewed by others
Abbreviations
- SP-A:
-
Surfactant protein A
- SNPs:
-
Single-nucleotide polymorphisms
- IgE:
-
Total serum immunoglobulin E
- AR:
-
Allergic rhinitis
- cRFLP:
-
Converted restriction fragment length polymorphism
- HWE:
-
Hardy–Weinberg equilibrium
- LD:
-
Linkage disequilibrium
- D:
-
Disequilibrium value
References
Von Mutius E (2004) Influences in allergy: epidemiology and the environment. J Allergy Clin Immunol 113:373–379
Vercelli D (2008) Advances in asthma and allergy genetics in 2007. J Allergy Clin Immunol 122:267–271
Broide D (2008) New perspectives on mechanisms underlying chronic allergic inflammation and asthma in 2007. J Allergy Clin Immunol 122:475–480
Ober C, Hoffjan S (2006) Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun 7:95–100
McCormack FX, Gibbons R, Ward SR et al (2003) Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem 278:36250–36256
Hohlfeld JM (2002) The role of surfactant in asthma. Respir Res 3:4
Malhotra R, Haurum J, Thiel S et al (1993) Pollen grains bind to lung alveolar type cells (A459) via lung surfactant protein A (SP-A). Biosci Rep 13:79–90
Wright JR (1997) Immunomodulatory functions of surfactant. Physiol Rev 77:931–962
Crouch EC (1998) Collectin and pulmonary host defense. Am J Respir Cell Mol Biol 19:177–201
Hohlfeld JM, Erpenbeck VJ, Krug N (2002) Surfactant proteins SP-A and SP-D as modulators of the allergic inflammation in asthma. Pathobiology 70:287–292
Gardai SJ, Xiao YQ, Dickinson M et al (2003) By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 115:13–23
Balis JU, Paterson JF, Paciga JE et al (1985) Distribution and subcellular localization of surfactant-associated glycoproteins in human lung. Lab Investig 52:657–669
Saitoh H, Okayama H, Shimura S et al (1998) Surfactant protein A2 gene expression by human airway submucosal gland cells. Am J Respir Cell Mol Biol 19:202–209
Wootten CT, Labadie RF, Chen A et al (2006) Differential expression of surfactant protein A in the nasal mucosa of patients with allergy symptoms. Arch Otolaryngol Head Neck Surg 132:1001–1007
Hoover RR, Floros J (1998) Organization of the human SP-A and SP-D loci at 10q22–23. Physical and radiation hybrid mapping reveals gene order and orientation. Am J Respir Cell Mol Biol 18:353–362
DiAngelo S, Lin Z, Wang G et al (1999) Novel, non-radioactive, simple and multiplex PCR-cRFLP methods for genotyping human SP-A and SP-D marker alleles. Dis Markers 15:269–281
Pantelidis P, Lagan AL, Davies JC et al (2003) A single round PCR method for genotyping human surfactant protein (SP)-A1, SP-A2 and SP-D gene alleles. Tissue Antigens 61:317–321
Haataja R, Ramet M, Marttila R et al (2000) Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome. Hum Mol Genet 9:2751–2760
Marttila R, Haataja R, Guttentag S et al (2003) Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins. Am J Respir Crit Care Med 168:1216–1222
Marttila R, Haataja R, Ramet M et al (2003) Surfactant protein A gene locus and respiratory distress syndrome in Finnish premature twin pairs. Ann Med 35:344–352
Lofgren J, Ramet M, Renko M et al (2002) Association between surfactant protein A gene locus and severe respiratory syncytial virus infection in infants. J Infect Dis 185:283–289
Madan T, Saxena S, Murthy KJ et al (2002) Association of polymorphisms in collagen region of human SP-A1 and SP-A2 genes with pulmonary tuberculosis in Indian population. Clin Chem Lab Med 40:1002–1008
Floros J, Lin HM, García A et al (2000) Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population. J Infect Dis 182:1473–1478
Malik S, Greenwood CM, Eguale T et al (2006) Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia. Hum Genet 118:752–759
Saxena S, Madan T, Shah A et al (2003) Association of polymorphisms in the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 111:1001–1007
Pettigrew MM, Gent JF, Zhu Y et al (2007) Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes. BMC Med Genet 8:15
Kang HJ, Choi YM, Chae SW et al (2006) Polymorphism of the CD14 gene in perennial allergic rhinitis. Int J Pediatr Otorhinolaryngol 70:2081–2085
Trikalinos TA, Salanti G, Khoury MJ et al (2006) Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations. Am J Epidemiol 163:300–309
Brandt EB, Mingler MK, Stevenson MD et al (2008) Surfactant protein D alters allergic lung responses in mice and human subjects. J Allergy Clin Immunol 121:1140–1150
Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98
Sanz C, Isidoro-García M, Dávila I et al (2006) Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma. Allergy 61:543–548
Wang G, Umstead TM, Phelps DS et al (2002) The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production. Environ Health Perspect 110:79–84
Nishiyama C, Akizawa Y, Nishiyama M et al (2004) Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy. J Immunol 173:6458–6464
Kabesch M, Tzotcheva I, Carr D et al (2003) A complete screening of the IL-4 gene: novel polymorphisms and their association with asthma and IgE in childhood. J Allergy Clin Immunol 112:893–898
Barnes KC (2000) Evidence for common genetic elements in allergic disease. J Allergy Clin Immunol 106:S192–S200
Holmskov U, Thiel S, Jensenius JC (2003) Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol 21:547–578
Mikerov AN, Wang G, Umstead TM et al (2007) Surfactant protein A2 (SP-A2) variants expressed in CHO cells stimulate phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants. Infect Immun 75:1403–1412
Mikerov AN, Umstead TM, Gan X et al (2008) Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants. Am J Physiol Lung Cell Mol Physiol 294:L121–L130
Oberley RE, Snyder JM (2003) Recombinant human SP-A1 and SP-A2 proteins have different carbohydrate-binding characteristics. Am J Physiol Lung Cell Mol Physiol 284:L871–L881
Wang G, Bates-Kenney SR, Tao JQ et al (2004) Differences in biochemical properties and in biological function between human SP-A1 and SPA2 variants, and the impact of ozone-induced oxidation. Biochemistry 43:4227–4239
Wang G, Phelps DS, Umstead TM et al (2000) Human SP-A protein variants derived from one or both genes stimulate TNF-alpha production in the THP-1 cell line. Am J Physiol Lung Cell Mol Physiol 278:L946–L954
Luan B, Han Y, Zhang X et al (2010) Association of the SDF1–3’A polymorphism with susceptibility to myocardial infarction in Chinese Han population. Mol Biol Rep 37(1):399–403
Cai LQ, Wang ZX, Lu WS et al (2010) A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population. Mol Biol Rep 37(1):389–394
Xu L, Qiao Y, Zhang X et al (2010) CCR2–64I allele is associated with the progression of AIDS in a Han Chinese population. Mol Biol Rep 37(1):311–316
Xia G, Pan F, Liao F et al (2010) No significant association between Fc receptor-like 3 gene polymorphisms and human leukocyte antigen-B27 positive ankylosing spondylitis in Han Chinese population. Mol Biol Rep 37(1):297–300
Liu XL, Zhang FL, Zhou ZY et al (2010) Analysis of two sequence variants in peroxisome proliferator activated receptor gamma gene in Tajik population at high altitudes and Han population at low altitudes in China. Mol Biol Rep 37(1):179–184
Li XX, Liu JP, Cheng JQ et al (2009) Intercellular adhesion molecule-1 gene K469E polymorphism and ischemic stroke: a case-control study in a Chinese population. Mol Biol Rep 36(6):1565–1571
Zhang X, Su D, Zhang X et al (2009) Association of ADAM33 gene polymorphisms with adult concomitant allergic rhinitis and asthma in Chinese Han population. Mol Biol Rep 36(6):1505–1509
Ramet M, Haataja R, Marttila R et al (2000) Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population. Am J Hum Genet 66:1569–1579
Jack DL, Cole J, Naylor SC et al (2006) Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease. Clin Infect Dis 43:1426–1433
Madan T, Kishore U, Singh M et al (2001) Lung surfactant protein A (SP-A) and D (SP-D) suppress eosinophilia and specific IgE antibodies in a murine model of fungal hypersensitivity. J Clin Invest 107:467–475
Deng YQ, Tao ZZ, Kong YG et al (2009) Association between single nucleotide polymorphisms of surfactant protein D and allergic rhinitis in Chinese patients. Tissue Antigens 73:546–552
Boehringer S, Jörg TE, Krawczak M (2000) Genetic association studies of bronchial asthma—a need for Bonferroni correction? Hum Genet 107:197
Acknowledgment
This work was supported by the national key technology R&D program (Grant number 2007BA18B15).
Author information
Authors and Affiliations
Corresponding author
Additional information
Yuqin Deng and Shiming Chen contributed equally to this study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Deng, Y., Chen, S., Chen, J. et al. Relationship between surfactant protein A polymorphisms and allergic rhinitis in a Chinese Han population. Mol Biol Rep 38, 1475–1482 (2011). https://doi.org/10.1007/s11033-010-0254-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-010-0254-4