Association of the MMP9 gene with childhood cedar pollen sensitization and pollinosis

Abstract

Matrix metalloproteinase 9 (MMP9) gene has been shown to be involved in the pathogenesis of allergic rhinitis (AR) and asthma. Previous studies suggested that single-nucleotide polymorphisms (SNPs) of the MMP9 gene conferred a risk for childhood asthma. However, whether the SNPs confer a risk for AR has not been previously investigated. The objective of this study was to investigate whether SNPs of the MMP9 gene are associated with risk of seasonal AR (pollinosis), perennial AR and allergen sensitization. A total of 670 school children were recruited in Japan and genotyped for functional polymorphism in the promoter (-1590C/T: rs3918242) and three amino-acid substitutions (R297Q: rs17576; P574R: rs2250889; R668Q: rs17577). Serum levels of total and specific IgE were determined. Disease status and other clinical characteristics of the subjects were investigated using a questionnaire. Associations between the MMP9 SNPs and both AR and serum IgE levels were evaluated. -1590C/T showed significant association with cedar pollinosis (corrected P (Pcor)¼0.039). R668Q was in strong linkage disequilibrium (LD) with -1590C/T and showed significant association with cedar pollinosis (Pcor¼0.023) and serum cedar pollen-specific IgE level (Pcor¼0.022). A haplotype associated with -1590T and 668Q showed a significant association with cedar pollinosis, orchard grass pollinosis and cedar pollen-specific IgE (Pcor¼0.0012, Pcor¼0.0059 and Pcor¼0.0041, respectively). R297Q and P574R were in weak LD with the rest of the SNPs and did not show significant association with disease. Compared with wild-type MMP9 protein (279R-574P-668R), a variant enzyme (279R-574P-668Q) that showed association with pollinosis had lower activity. However, lower enzyme activity was not associated with disease risk because another variant (279Q-574R-668R) showed lower enzyme activity but was not associated with pollinosis. The -1590T allele and its corresponding haplotype was associated with higher promoter activity and with pollen-specific IgE levels and pollinosis, suggesting that -1590C/T may have more impact on sensitization and disease development than R668Q. Our results suggest that the MMP9 gene confers susceptibility to cedar pollinosis in Japanese children. The MMP9 gene may be associated with pollinosis through sensitization processes. Journal of Human Genetics (2012) 57, 176-183; doi:10.1038/jhg.2011.148; published online 12 January 2012 Keywords: allergic rhinitis; association; cedar pollinosis; haplotype; matrix metalloproteinase; MMP9 gene; serum IgE; SNP INTRODUCTIONThe main symptoms of allergic rhinitis (AR) are nasal congestion caused by mucosal edema; runny nose caused by hypersecretion; and repetitive sneezing. Pollinosis is a seasonal type of AR caused by an allergic reaction to pollen. Japanese cedar pollen is the most common causative allergen for pollinosis in Japan. According to a recent study, the prevalence rates of AR and cedar pollinosis in 2006 were 27.2 and 8.0%, respectively; both of which were higher than the rates in 1996. 1...

The Influence of Functional Polymorphisms in Matrix Metalloproteinase 9 on Survival of Breast Cancer Patients in a Chinese Population

“…The presence of the combined rs17577GG and rs3787268 GA + AA genotypes for both ER + and HER-2 -patients might jointly decrease DFS and DDFS. This SNP was also shown to be related to the risk of skin squamous cell carcinoma (Nan et al, 2008), endometriosis (Han et al, 2009), nasal polyposis (Wang et al, 2010), and childhood pollinosis (Inoue et al, 2012). Moreover, the A allele in rs17577 was proven to improve survival of nonsmall-cell lung cancer patients ( Jin et al, 2009) similar to our result.…”

“…This missense mutation is located in the hemopexin-like domain and probably functions in substrate binding (Li et al, 1995), and through in silico molecular modeling, it was suggested that this mutation may alter MMP9 activity by interacting with PEX9 and TIMP1 (Rodius et., 2011). It is worth noting that this tagging SNP is in a strong LD with an MMP9 promoter SNP, rs3918242 ( -1562C > T) (Han et al, 2009;Jin et al, 2009;Wang et al, 2010;Inoue et al, 2012), which might alter the MMP9 gene transcriptional activity and influence the enzyme production (Zhang et al, 1999). Taken together, these studies imply that rs17577 is likely to have influence in some subgroups of breast cancer patients through MMP9-related tumor invasion and metastasis.…”

Extracellular matrix remodeling genes polymorphisms and risk of chronic bronchitis and recurrent pneumonia in children

“…37 MMP9 polymorphisms were also associated with allergic rhinitis in children. 38 The results of our study suggest that MMP9 can be involved in the pathogenesis of not only allergic diseases but also of other inflammatory disorders of the respiratory system in children.…”

“…37 There have been several studies analyzing the association of MMP9 polymorphisms with respiratory diseases. 30,[35][36][37][38] For instance, an analysis of 17 MMP9 polymorphisms in Japanese children with atopic asthma showed that the disease risk was associated with certain MMP9 genotypes. 37 MMP9 polymorphisms were also associated with allergic rhinitis in children.…”

Matrix Metalloproteinase-9 Gene Polymorphisms and Chronic Kidney Disease

“…It is possible that substitution of the positively charged arginine to an uncharged glutamine may influence inhibitor binding and progelatinase activation. Similarly, subjects with MMP9 668Q showed greater MMP-9 activation [26]. Accordingly, MMP9 668Q was associated with a reduced risk for allograft rejection [27].…”