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박흥우,송우정,조상헌,Michael J. McGeachie,Fernando Martinez,Dave Mauger,Bruce G. Bender,Kelan G. Tantisira 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 topranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects. We identified two nodes (depression and rs4672619 mapping to ERBB4 (Erb-B2 receptor tyrosine kinase 4)) that were within the Markov neighborhood of the symptom node in the network and then evaluated the interactive effects of depressive status and rs4672619 genotypes on asthma symptom severity. In childhood asthmatics with homozygous reference alleles, severe depression was related to less severe symptoms. However, in childhood asthmatics with heterozygous alleles and homozygous variant alleles, depression and symptom severity showed a positive correlation (interaction permutation P value = 0.019). We then tried to evaluate whether the interactive effects that we found were sustained in another independent cohort of elderly asthmatics. Contrary to the findings from childhood asthmatics, elderly asthmatics with homozygous reference alleles showed a positive correlation between depression and symptom severity, and elderly asthmatics with heterozygous alleles and homozygous variant alleles showed a negative correlation (interaction permutation P value = 0.003). In conclusion, we have identified a novel SNP, rs4672619, that shows interactive effe
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Tiwari Anshul,Wang Alberta L.,Li Jiang,Lutz Sharon M.,Kho Alvin T,Weiss Scott T,Tantisira Kelan G,McGeachie Michael J. 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.4
Objective MicroRNAs (miRs) are small non-coding RNA molecules of around 18–22 nucleotides that are key regulators of many biologic processes, particularly inflammation. The purpose of this study was to determine the association of circulating miRs from asthmatic children with seasonal variation in allergic inflammation and asthma symptoms. Methods We used available small RNA sequencing on blood serum from 398 children with mild-to-moderate asthma from the Childhood Asthma Management Program. We used seasonal asthma symptom data at the study baseline and allergen affection status from baseline skin prick tests as primary outcomes. We identified differentially expressed (DE) miRs between pairs of seasons using DESeq2. Regression analysis was used to identify associations between allergy status to specific seasonal allergens and DE miRs in 4 seasons and between seasonal asthma symptom data and DE miRs. We performed pathway enrichment analysis for target genes of the DE miRs using DAVID. Results After quality control, 398 samples underwent differential analysis between the 4 seasons. We found 52 unique miRs from a total of 81 DE miRs across seasons. Further investigation of the association between these miRs and sensitization to seasonal allergens using skin prick tests revealed that 26 unique miRs from a total of 38 miRs were significantly associated with a same-season allergen. Comparison between seasonal asthma symptom data revealed that 2 of these 26 miRs also had significant associations with asthma symptoms in the same seasons: miR-328-3p (P < 0.03) and let-7d-3p (P < 0.05). Enrichment analysis showed that the most enriched pathway clusters were Rap1, Ras, and MAPK signaling pathways. Conclusion Our results show seasonal variation in miR-328-3p and let-7d-3p are significantly associated with seasonal asthma symptoms and seasonal allergies. These indicate a potentially protective role for let-7d-3p and a deleterious role for miR-328-3p in asthmatics sensitized to mulberry. Further work will determine whether these miRs are drivers or results of the allergic response.
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