PT  - JOURNAL ARTICLE
AU  - Rumana Siddique
AU  - Hongmei Zhang
AU  - Hasan Arshad
AU  - John Holloway
AU  - Wilfried Karmaus
TI  - Interactions of genetic variants and DNA-M of <em>TSLP</em> modify the eczema risk
AID  - 10.1183/13993003.congress-2016.PA1210
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA1210
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA1210.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA1210.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Background: Eczema is suggested to result from interplay of environmental factors, genetic variants (SNP) and DNA methylation (DNA-M). TSLP (Thymic Stromal Lymphopoietin) is considered a candidate gene for eczema.Objective: To analyze the risk of eczema, we explored the interaction of SNPs and cytosine-guanine-phosphate (CpG) sites of TSLP in two subsequent generations.Method: Data was collected from three-generation birth cohort (F0, F1 and F2, Isle of Wight) including questionnaire, DNA-M (370 samples at age 18 of F1, 129 cord blood sample of F2) using Illumina Infinium HumanMethylation450 array, and SNP data using the HumanOmniExpress BeadChip. Nine SNPs and 12 CpG sites were analyzed. Interactions of 6 SNPs and CpGs were considered for further analysis. Log-linear models were used to estimate risk ratios (RR) including the interaction term.Results: In both generations we observed statistically significant interactions of one CpG with 3 SNPs. The rs1837253 x cg15089387 increased risk of eczema in F1 and F2; RR=23.54, 95%CI 2.37-234.66, p-value (P) =0.0071 and RR=22.04, 95%CI 1.65-293.48, P=0.0192 respectively. The rs3806932 x cg15089387 also increased the risk in both generations (RR=5.76, 95%CI 1.12-29.68, P=0.0363 in F1 and RR=6.3, 95%CI 1.44-27.6, P=0.0147 in F2). However, rs3806933 x cg15089387 shows an opposite direction in F1 and F2 (RR=0.003, 95% CI 0.00015, 0.061, P = 0.0002 in F1 and RR=11.84, 95%CI 3.22-43.51, P=0.0042 in F2). Regarding the latter two SNPs, the CpG was found to be located in between both.Conclusion: It is important to further study the interaction of SNPs and CpGs on the TSLP gene to explore conflicting and compatible results explaining the role of TSLP as risk factor for eczema.