Article

Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans

Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 11/2009; 125(2):321-327.e13. DOI: 10.1016/j.jaci.2009.09.007
Source: PubMed

ABSTRACT More than 200 asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs).
We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population.
From the literature, we identified candidate genes with at least 1 positive report of association with asthma phenotypes in human subjects or implicated in asthma pathogenesis using knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 550v3 BeadChip. Separate candidate gene analyses were performed for 2933 autosomal SNPs in the 237 selected genes by using the log-linear method with a log-additive risk model.
Sixty-one of the 237 genes had at least 1 SNP with a P value of less than .05 for association with asthma. The 9 most significant results were observed for rs2241715 in the gene encoding TGF-beta1 (TGFB1; P = 3.3 x 10(-5)), rs13431828 and rs1041973 in the gene encoding IL-1 receptor-like 1 (IL1RL1; P = 2 x 10(-4) and 3.5 x 10(-4)), 5 SNPs in the gene encoding dipeptidyl-peptidase 10 (DPP10; P = 1.6 x 10(-4) to 4.5 x 10(-4)), and rs17599222 in the gene encoding cytoplasmic FMR1 interacting protein 2 (CYFIP2; P = 4.1 x 10(-4)). False discovery rates were less than 0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma.
This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes, including TGFB1, IL1RL1, IL18R1, and DPP10, might contribute to childhood asthma susceptibility in a Mexican population.

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    • "It binds to specific voltage-gated potassium channels, altering their structures and biophysical properties,15 but the cellular functions of DPP10 remain unknown. DPP10 has been linked to asthma susceptibility by several genome-wide association studies,16,17 and recently impaired expression of DPP10 gene in malignant mesothelioma18 and nasopharyngeal carcinoma has been reported.19 "
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    ABSTRACT: Purpose The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. Materials and Methods The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes. Results DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008). Conclusion DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.
    Yonsei medical journal 11/2013; 54(6):1362-9. DOI:10.3349/ymj.2013.54.6.1362 · 1.26 Impact Factor
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    • "Further allergy-related phenotypes susceptibility genes have been discovered by GWAS as chromosome 5q12 at the region of the phosphodiesterase 4D (PDE4D) (Himes et al., 2009) involved in way smooth muscle concentration, an association with asthma and chromosome 1, at the region of DENND1B (gene that encodes for a protein that interact s with the TNF-α receptor) (Sleiman & Hakonarson , 2010). Using GWASs significant evidences were observed for asthma association and several genes as DPP10 (Mathias et al., 2010), TGFB1, IL1RL1 and CYFIP2 (Wu et al., 2010). "
    Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment, 03/2012; , ISBN: 978-953-51-0227-4
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    • "Further allergy-related phenotypes susceptibility genes have been discovered by GWAS as chromosome 5q12 at the region of the phosphodiesterase 4D (PDE4D) (Himes et al., 2009) involved in way smooth muscle concentration, an association with asthma and chromosome 1, at the region of DENND1B (gene that encodes for a protein that interact s with the TNF-α receptor) (Sleiman & Hakonarson , 2010). Using GWASs significant evidences were observed for asthma association and several genes as DPP10 (Mathias et al., 2010), TGFB1, IL1RL1 and CYFIP2 (Wu et al., 2010). "
    03/2012; , ISBN: 978-953-51-0227-4
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