Limits...
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: 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.

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

Flow chart on study sample selection from the Boston Birth Cohort.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4257764&req=5

fig01: Flow chart on study sample selection from the Boston Birth Cohort.

Mentions: A total of 1219 children from the BBC were initially genotyped for 1188 SNPs. Detailed information on the recruitment of BBC has been described previously [22]. In this study, we specifically focused on subjects who have both genotypic data and data on allergic sensitization. As shown in Figure 1, there are a total of 756 children from BBC with 1188 SNPs genotyped by the Illumina HumanOmni-Quad Beadchip. Of these, 125 subjects were further removed because of failure in quality control (QC) measures. In addition, we removed 293 SNPs because of one or more of the followings: (1) minor allele frequency (MAF) ≤5% (n = 52), (2) Hardy–Weinberg equilibrium (HWE) P-value <0.001 (n = 148), (3) SNPs in strong linkage disequilibrium (LD—r2 ≥ 0.8; n = 118), and (4) SNPs with 2 or more than 2 mentioned criteria above (n = 25) [23]. Thus, our final analysis was performed in 631 subjects consisting of allergen sensitized (AS, n = 207) and non-sensitized to environmental allergens (n = 424; Table1) with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes (Table S1). Allergic sensitization was defined as at least 1 positive allergen-specific IgE measurement. These allergic individuals incldued those who are sensitized to: (1) cockroach allergen (n = 75), (2) dermatophagoides Pteronyssinus (n = 99), Dermatophagoides Farinae (N = 33), (3) alternaria alternata (n = 89), (4) danger to dog (n = 79), and (6) cat (n = 60) (Fig. 1). For the black population, there were 132 allergic sensitized and 259 were non-sensitized subjects. Among these subjects with allergic sensitization, a total of 48 subjects were sensitized to cockroach, 59 were sensitized to house dust mite, and 160 were sensitized to others (Table1, Table S2). Among those subjects, the most common races are Black (62.1%), Hispanic (21.7%), and White (5.1%), Cap Verdean (5.1%), respectively. The rest are less than 5% (Asian/Pacific Islander, Caribbean, and unknown, Table2). The study protocols were approved by the Institutional Review Boards (IRBs) of Children's Memorial Hospital in Chicago and Boston University Medical Center. A data repository protocol of the BBC was approved by the Johns Hopkins Bloomberg School of Public Health IRB. All participating families provided written informed consent.


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)

Flow chart on study sample selection from the Boston Birth Cohort.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Flow chart on study sample selection from the Boston Birth Cohort.
Mentions: A total of 1219 children from the BBC were initially genotyped for 1188 SNPs. Detailed information on the recruitment of BBC has been described previously [22]. In this study, we specifically focused on subjects who have both genotypic data and data on allergic sensitization. As shown in Figure 1, there are a total of 756 children from BBC with 1188 SNPs genotyped by the Illumina HumanOmni-Quad Beadchip. Of these, 125 subjects were further removed because of failure in quality control (QC) measures. In addition, we removed 293 SNPs because of one or more of the followings: (1) minor allele frequency (MAF) ≤5% (n = 52), (2) Hardy–Weinberg equilibrium (HWE) P-value <0.001 (n = 148), (3) SNPs in strong linkage disequilibrium (LD—r2 ≥ 0.8; n = 118), and (4) SNPs with 2 or more than 2 mentioned criteria above (n = 25) [23]. Thus, our final analysis was performed in 631 subjects consisting of allergen sensitized (AS, n = 207) and non-sensitized to environmental allergens (n = 424; Table1) with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes (Table S1). Allergic sensitization was defined as at least 1 positive allergen-specific IgE measurement. These allergic individuals incldued those who are sensitized to: (1) cockroach allergen (n = 75), (2) dermatophagoides Pteronyssinus (n = 99), Dermatophagoides Farinae (N = 33), (3) alternaria alternata (n = 89), (4) danger to dog (n = 79), and (6) cat (n = 60) (Fig. 1). For the black population, there were 132 allergic sensitized and 259 were non-sensitized subjects. Among these subjects with allergic sensitization, a total of 48 subjects were sensitized to cockroach, 59 were sensitized to house dust mite, and 160 were sensitized to others (Table1, Table S2). Among those subjects, the most common races are Black (62.1%), Hispanic (21.7%), and White (5.1%), Cap Verdean (5.1%), respectively. The rest are less than 5% (Asian/Pacific Islander, Caribbean, and unknown, Table2). The study protocols were approved by the Institutional Review Boards (IRBs) of Children's Memorial Hospital in Chicago and Boston University Medical Center. A data repository protocol of the BBC was approved by the Johns Hopkins Bloomberg School of Public Health IRB. All participating families provided written informed consent.

Bottom Line: 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.

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