Gene - Gene Interactions AmongMCPGenes Polymorphisms in Asthma

Abstract

PurposeMonocyte chemoattractant proteins (MCPs) are important cytokines that involved in cellular activation and releasing of inflammatoy mediators by basophils and eosinophils in allergic disease. Some MCP gene variants implicate in asthma and monoclonal antibody for MCP-3 blocks allergic inflammations in the patients with asthma. Detection of interactions between gene and environment or between genes for complex disease such as asthma is important. We searched for an evidence of genetic effect of single nucleotide polymorphisms (SNPs) of MCP genes as well as gene - gene interactions involved in asthma.MethodsFour hundreds asthmatics and four hundreds normal controls were enrolled. Asthma was defined as a positive bronchodilator response or positive methacholine provocation test with compatible clinical symptoms. Seven MCP gene SNPs (2 SNPs in MCP-1, 1 in MCP-2, and 4 in MCP-3) were included. Association analyses between SNP and asthma, and the tests for gene - gene interaction were performed.ResultsStrong linkage disequilibria were found among 7 MCP gene polymorphisms. There was no SNP that showed a significant association with asthma among 7 SNPs of 3 MCP genes. No haplotype was associated with asthma, either. The combination of MCP1-2518G>A, MCP2+46A>C, and MCP3+563C>T was the best predictive model for asthma as compared to the control in tests for gene - gene interaction. The MCP1-2518G>A and MCP2+46A>C was the second best predictive combination and this had the highest synergistic interaction effect on the subject's status than any other combination of polymorphisms. Complete linkages were not associated with the gene - gene interactions models.ConclusionsMCP gene polymorphisms probably interact with each other; thus, these findings may help in developing a possible genetic marker to predict asthma.

Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms

“…MCP-1 stimulated trafficking of ATX to vesicles (Fig. 4A) and it can be anticipated that polymorphisms in the MCP-1 gene (Lee and Park, 2014) might influence the in vivo response. Functional polymorphisms for P2X7 (Ghalali et al, 2014) and P2X4 (Gu et al, 2013) individuals (Gui et al, 2014) and studies of P2X7 and P2X4 might be of interest because they have been implicated in other sensitization events.…”

Environmental Exposure and Genetic Predisposition as Risk Factors for Asthma in China

“…A series of studies have given considerable attention to the idea that genetic polymorphism might contribute to the development of asthma and may possibly be one of the reasons for these difference. 49 50 51 Liu found that the genotype and allele frequencies of the 2 SNPs Rs2289276 and Rs2289278 in the TSLP were significantly different between Chinese Han asthma patients and the healthy controls. The C allele of rs2289278 showed a close association with the decrease in FEV1:FVC.…”

Association between MCP-1 -2518A>G polymorphism and asthma susceptibility: a meta-analysis

“…They found that the MCP-1 -2518 G polymorphism was correlated with asthma severity, and their results were subsequently supported by Keszei et al (15) and Tolgyesi et al (16). In contrast, two studies reported a protective effect of allele MCP-1 -2518 G polymorphism in asthmatic children (17,18), and three studies showed no significant association between MCP-1 -2518 G polymorphism and asthma risk (13,14,19). Our meta-analysis provided a more precise estimation based on a larger sample size compared with the individual study.…”

“…Of these, 5 articles were excluded because 3 articles were irrelevant, 1 article lacked a case-control design, and 1 article focused on another MCP-1 SNP site. Eventually, we identified 8 case-control publications, including 1562 asthma patients and 1574 controls, to evaluate the association of MCP-1 -2518 A>G polymorphism with asthma susceptibility (12–19). There were three studies performed in Caucasian, three in Asian, and two in African populations.…”