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Genetic determinants in the development of sensitization to environmental allergens in early childhood.

Tripathi P, Hong X, Caruso D, Gao P, Wang X - Immun Inflamm Dis (2014)

Bottom Line: Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008).Some of findings were further validated when analysis was limited to black population.Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.

View Article: PubMed Central - PubMed

Affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine Baltimore, Maryland, 21224.

ABSTRACT
Sensitization to environmental allergens remains one of the strongest risk factors for asthma, and there is likely a genetic basis. We sought to identify genetic determinants for the development of allergic sensitization to environmental allergens, particularly cockroach allergen, in early childhood. A total of 631 children with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes were selected from an existing dataset (Boston Birth Cohort). Genetic analysis was performed for allergic sensitizations among all subjects and sub-population, Black/African, respectively. Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008). When analyses were specifically performed for cockroach sensitization, 16 SNPs in 13 genes showed P < 0.05, including five genes with SNPs at P < 0.01 (JAK1, JAK3, IL5RA, FCER1A, and ADAM33). Particularly, haplotype analyses demonstrated that multiple-haplotypes in FCER1A were significantly associated with cockroach sensitization with the strongest association for a 2-marker haplotype (rs6665683T-rs12136904T, P = 0.001). Furthermore, SNP rs6665683 was marginally associated with the levels of cockroach allergen specific IgE. When a similar analysis was performed for house dust mite, four SNPs in three genes (JAK2, MAML1, and NOD1) had P < 0.01. Of these, JAK2 appeared to be an only gene showing association across the sensitizations we analyzed. Some of findings were further validated when analysis was limited to black population. Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.

No MeSH data available.


Related in: MedlinePlus

The −log10 (P value) for associations of genotyped SNPs with (A) allergic sensitization, (B) cockroach allergen, and (C) house dust mite. The x-axis represents individual SNP. The gray line represents P = 0.05.
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fig02: The −log10 (P value) for associations of genotyped SNPs with (A) allergic sensitization, (B) cockroach allergen, and (C) house dust mite. The x-axis represents individual SNP. The gray line represents P = 0.05.

Mentions: We examined the association between those genotyped SNPs and allergic sensitization (Table3, Fig. 2A). A total of 8 SNPs in or near seven genes showed P < 0.05. Of these, three SNPs had P < 0.01, including rs7851969 in JAK2 [Odds ratio (OR) (95% CI), 2.08 (1.29–3.37), P = 0.003], rs11739089 in CNOT6 [OR (95% CI), 1.54 (1.17–2.11), P = 0.008], and rs6627 in MAML1 [OR (95% CI), 0.70 (0.54–0.92), P = 0.009]. Furthermore, several candidate genes also showed significant association with allergic sensitization, including IL4R (rs3024633, rs3024576), JAK1 (rs7524842), IL12B (rs3212227), and IL5RA (rs163550). When the same analyses was limited to black population, we found that, except for SNPs in gene MAML1 and IL5RA, the associations we observed for others in total population still remained. Of these, SNP rs11739089 in CNOT6 showed even stronger association in the black population (P = 0.001).


Genetic determinants in the development of sensitization to environmental allergens in early childhood.

Tripathi P, Hong X, Caruso D, Gao P, Wang X - Immun Inflamm Dis (2014)

The −log10 (P value) for associations of genotyped SNPs with (A) allergic sensitization, (B) cockroach allergen, and (C) house dust mite. The x-axis represents individual SNP. The gray line represents P = 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257764&req=5

fig02: The −log10 (P value) for associations of genotyped SNPs with (A) allergic sensitization, (B) cockroach allergen, and (C) house dust mite. The x-axis represents individual SNP. The gray line represents P = 0.05.
Mentions: We examined the association between those genotyped SNPs and allergic sensitization (Table3, Fig. 2A). A total of 8 SNPs in or near seven genes showed P < 0.05. Of these, three SNPs had P < 0.01, including rs7851969 in JAK2 [Odds ratio (OR) (95% CI), 2.08 (1.29–3.37), P = 0.003], rs11739089 in CNOT6 [OR (95% CI), 1.54 (1.17–2.11), P = 0.008], and rs6627 in MAML1 [OR (95% CI), 0.70 (0.54–0.92), P = 0.009]. Furthermore, several candidate genes also showed significant association with allergic sensitization, including IL4R (rs3024633, rs3024576), JAK1 (rs7524842), IL12B (rs3212227), and IL5RA (rs163550). When the same analyses was limited to black population, we found that, except for SNPs in gene MAML1 and IL5RA, the associations we observed for others in total population still remained. Of these, SNP rs11739089 in CNOT6 showed even stronger association in the black population (P = 0.001).

Bottom Line: Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008).Some of findings were further validated when analysis was limited to black population.Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.

View Article: PubMed Central - PubMed

Affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine Baltimore, Maryland, 21224.

ABSTRACT
Sensitization to environmental allergens remains one of the strongest risk factors for asthma, and there is likely a genetic basis. We sought to identify genetic determinants for the development of allergic sensitization to environmental allergens, particularly cockroach allergen, in early childhood. A total of 631 children with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes were selected from an existing dataset (Boston Birth Cohort). Genetic analysis was performed for allergic sensitizations among all subjects and sub-population, Black/African, respectively. Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008). When analyses were specifically performed for cockroach sensitization, 16 SNPs in 13 genes showed P < 0.05, including five genes with SNPs at P < 0.01 (JAK1, JAK3, IL5RA, FCER1A, and ADAM33). Particularly, haplotype analyses demonstrated that multiple-haplotypes in FCER1A were significantly associated with cockroach sensitization with the strongest association for a 2-marker haplotype (rs6665683T-rs12136904T, P = 0.001). Furthermore, SNP rs6665683 was marginally associated with the levels of cockroach allergen specific IgE. When a similar analysis was performed for house dust mite, four SNPs in three genes (JAK2, MAML1, and NOD1) had P < 0.01. Of these, JAK2 appeared to be an only gene showing association across the sensitizations we analyzed. Some of findings were further validated when analysis was limited to black population. Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.

No MeSH data available.


Related in: MedlinePlus