CD14 and IL4R gene polymorphisms modify the effect of day care attendance on serum IgE levels

Suzuki, Yôichi; Hattori, Satoshi; Mashimo, Yoichi; Funamizu, Makiko; Kohno, Yoichi; Okamoto, Yoshitaka; Hata, Akira; Shimojo, Naoki

doi:10.1016/j.jaci.2009.03.035

Cited by 14 publications

(12 citation statements)

References 9 publications

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“…A total of 473 school children aged 6-12 years were enrolled in Chiba city in Chiba prefecture, details of which were described previously, 19 and 260 school children within the same age range were enrolled in Hokoto city in Yamanashi prefecture. Blood samples were collected for serum IgE measurement and DNA preparation from 410 children in Chiba and 260 children in Yamanashi in July and August 2006.…”

Section: Materials and Methods Subjectsmentioning

confidence: 99%

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

et al. 2012

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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...

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Section: Materials and Methods Subjectsmentioning

confidence: 99%

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

et al. 2012

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“…Compared to gene–environment interactions for asthma, there appear to be considerably fewer publications, which describe gene–environment interactions for atopy; for this review, five papers [(29), p. 138; Jan-144; (35), p. 593–602; (36), p. 231–6.e1–5; (37), p. 621–630; (38), p. 430–437] and one letter [(39), p. 1408–11.e1] were identified, Table 2. All the publications describe associations between variants in genes whose products are part of the adaptive or innate immune system.…”

Section: Gene–environment Interactions For Atopymentioning

confidence: 99%

Gene–Environment Interactions—What Can These Tell Us about the Relationship between Asthma and Allergy?

Turner

2017

Front. Pediatr.

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Asthma is a common condition, which is associated with atopy and allergic conditions including hay fever, eczema, and food allergies. Asthma and atopy are both complex conditions where genetic and environmental factors are implicated in causation. Interactions between genetic and environmental factors, likely via epigenetic mechanisms, are widely thought to be important in determining the risk for developing asthma and atopy. The nature of the relationship between asthma and atopy is unclear and the answer to the question “does atopy cause asthma?” remains unknown. This review explores the relationship between asthma and atopy from a gene–environment interaction perspective and tackles the question “are similar gene–environment interactions present for asthma and atopy?” The main finding is that gene–environment interactions are described for asthma and atopy in children but these interactions are seldom sought for both asthma and atopy in the same population. In the few instances where a gene–environment interaction is related to both asthma and atopy, there is no consistent evidence that similar interactions are common to asthma and atopy. Many plausible gene–environment interactions for asthma and atopy are yet to be explored. Overall, from the gene–environment interaction perspective, there is absence of evidence to better understand the complex relationship between asthma and atopy.

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“…Whereas, in our recent association study carried out on the same school children, these two gene variants had a modifying effect on the levels of total IgE later in life depending on the children's attendance of day care before 2 years of age. 15 This association could be detected because the day care attendance was taken in consideration as an environmental factor and the effect of a gene was investigated simultaneously with the effect of the other one.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical characteristics of this population as well as inclusion and exclusion criteria have been described previously. 15 In brief, after the exclusion of questionnaire-assessed asthma and/ or atopic dermatitis subjects and those with congenital heart diseases and lung diseases caused by premature birth, 336 children having a complete set of information on the total and eight specific IgE levels, genotypes and environmental factors were assigned to the child control group. The mean ages (range) of the four groups were as follows: childhood asthma, 9.9 (4-15); adult asthma, 45 (16-83); child controls, 9.3 (6-12); and adult control, 43.7 (20-75) years.…”

Section: Study Populationmentioning

confidence: 99%

Replication of genetic association studies in asthma and related phenotypes

et al. 2010

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In asthma genetics, the association of highly replicated susceptibility genes lacks consistency across populations. To identify genuine associations, we investigated the reproducibility of the 23 most promising asthma and asthma-related candidate genes in a moderately sized sample from the Japanese population. We compared the frequency of 33 polymorphisms in unrelated cases and controls and tested for their association with asthma, atopy and serum total IgE levels using allele frequency, codominant, dominant and recessive genotype models. On the basis of the consistency of our findings with previous metaanalyses and large replication studies, IL13, TNF, ADAM33, IL4RA and TBXA2R might represent common major asthma and asthma-related trait genes. Individual gene assessment was extended to the interactions between two polymorphisms using our original method. Interactions between TBXA2R and ADAM33, and IL4RA and C3 were suggested to increase the risk for childhood and all asthma (adult and childhood asthma combined). The confirmation of previously reported associations between gene polymorphisms and phenotypes was problematic when as few as several hundred samples per group were used. Stratification of the subjects by environmental factors or other confounding factors may be necessary to improve the sensitivity and reliability of association results. Keywords: association; asthma; atopy; polymorphism; replication INTRODUCTIONAsthma is a heritable trait 1 and investigations to determine the genetic components underlying asthma using linkage mapping and the candidate gene approach have been carried out. By 2006, more than 100 genes were associated with asthma and asthma-related phenotypes; 2 25 of these genes have been replicated in more than six independent association studies. In 2008, this list was complemented with an additional three genes, FLG, NAT2 and CCL15. 3 However, no single polymorphic marker or gene locus has been unanimously labeled as a strong and independent genetic determinant of asthma, and the results for the highly replicated genes have been inconsistent across the tested populations. 3 To identify true associations, it is of critical importance to comprehensively replicate the initial finding. 4 To this aim, we investigated whether the 23 most replicated genes for asthma and asthma-related phenotypes were positively associated with extrinsic childhood and adult asthma, atopy and total serum IgE levels in a moderately sized sample drawn from the Japanese population.We also tested eight genes that were significantly associated with asthma in our subjects: IL13, 5 TBXA2R, 6 GSTP1, 7 ADAM33, 8 MMP9, 9 IL12B, 10 C3 11 and SOCS1. 12 The re-evaluation of these associations is

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CD14 and IL4R gene polymorphisms modify the effect of day care attendance on serum IgE levels

Cited by 14 publications

References 9 publications

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

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

Gene–Environment Interactions—What Can These Tell Us about the Relationship between Asthma and Allergy?

Replication of genetic association studies in asthma and related phenotypes

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