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Global Translational Medicine Inflammatory gene-environment interactions in COPD

Table 8. Gene‑gene combinations of inflammatory gene loci associated with COPD in patients stratified by smoking status
Pattern COPD patients Healthy individuals P‑value P OR 95% CI
FDR
Smokers
IL19 rs2243193*A + IL4 rs2243250*C + PPBP rs352010*T 0.081 0.255 9.11e-11 2.77e-07 0.25 0.16 – 0.40
IL20 rs2981573*AA + IL19 rs2243193*A 0.046 0.233 2.36e-10 2.39e-07 0.21 0.12 – 0.36
IL12A rs568408*G + IL4 rs2243250*C + PPBP rs352010*TC 0.109 0.423 3.13e-10 1.90e-07 0.29 0.19 – 0.44
IL19 rs2243193*A + IL4 rs2243250*C + PPBP rs352010*TC 0.071 0.288 4.86e-10 2.11e-07 0.25 0.15 – 0.40
IL12B rs3212227*A + IL12A rs2243115*T + IL4 rs2243250*C + 0.121 0.328 1.36e-09 2.43e-07 0.28 0.18 – 0.43
PPBP rs352010*T
IL19 rs2243193*A + PPBP rs352010*T + FASLG rs763110*C 0.086 0.238 1.38e-09 2.33e-07 0.30 0.19 – 0.45
IL19 rs2243193*A + IL12A rs2243115*T + C5 rs17611*G + PPBP 0.075 0.228 2.03e-09 2.8e-07 0.27 0.17 – 0.43
rs352010*T
IL12A rs2243115*T + IL4 rs2243250*C + TGFb1 rs1800469*C + 0.133 0.314 5.39e-09 3.81e-07 0.33 0.22 – 0.49
PPBP rs352010*T
IL12A rs2243115*G + FAS rs1800682*AA 0.12 0.039 1.35e-05 6.46e-05 3.33 1.87 – 5.92
IL4 rs2070874*CC + PPBP rs352010*TT 0.10 0.034 4.57e-05 0.00017 3.14 1.74 – 5.65
FAS rs1800682*A + PPBP rs352010*TT 0.081 0.025 0.000134 0.0004 3.49 1.74 – 6.98
IL4 rs2243250*T + IL24 rs291107*T 0.395 0.31 0.00615 0.011 1.56 1.19 – 1.97
Non-smokers
IL12RB2 rs3762317*A + IL12A rs2243115*G + IL4 rs2070874*C + 0.333 0.026 1.3e-06 0.022 18.5 4.09 – 83.63
IL4RA rs1805010*A
IL12A rs2243115*G + IL4RA rs1805010*A + IL24 rs291107*T 0.35 0.062 1.37e-05 0.022 8.04 2.83 – 22.84
IL12A rs2243115*T + IL24 rs291107*C + PPBP rs352010*C 0.415 0.763 1.97e-05 0.017 0.22 0.10 – 0.45
IL19 rs2243193*A + IL12A rs2243115*T + IL24 rs291107*C + 0.175 0.519 3.45e-05 0.017 0.19 0.08 – 0.44
FASLG rs763110*C
IL12A rs2243115*T + IL24 rs291107*C 0.492 0.802 7.74e-05 0.016 0.23 0.11 – 0.49
IL19 rs2243193*G + IL12A rs568408*A + IL24 rs291107*T + PPBP 0.52 0.202 0.0002 0.023 4.26 1.92 – 9.41
rs352010*C
P, P value for Fisher’s test, P cor-FDR , P value after the FDR test.

decreased smoking index in smokers. The data obtained Significant associations of IL4 (rs2243250, rs2070874)
indicate a possible interaction of PPBP (rs352010) with loci and COPD were observed. IL4 (rs2243250) was
smoking. Moreover, CT and TT genotypes of PPBP associated with COPD only in smokers, and minor T
(rs352010) were associated with low levels of FVC, allele and TT genotype were identified as COPD risk
which characterize the degree of airway obstruction in markers. Haplotype analysis demonstrated that frequency
COPD and disease progression. Analysis of gene-gene of T-C haplotype by the rs2243250 and rs2070874 of IL4
interaction of inflammatory genes loci with COPD gene was higher among smoking patients with COPD.
risk in groups stratified by smoking status determined Moreover, IL4 (rs2243250) TT genotype was associated
that the T allele or CT genotype of PPBP (rs352010) with decreased FVC value. Gene-gene interaction analysis
gene was the key components of several combinations showed that the C allele of IL4 (rs2243250) was observed
associated with low risk of COPD in smokers, while in several patterns associated with low risk of COPD in
the TT genotype of PPBP (rs352010) along with the smokers and in one combination in non-smokers. IL4
CC genotype of IL4 (rs2070874) or with A allele of FAS (rs2070874) was associated with COPD both in smokers
(rs1800682) genes was associated with increased risk of and non-smokers; minor T allele and TT genotype were
COPD in smokers. PPBP codes for PPBP and is located identified as protective markers. TT genotype of rs2070874
at chromosome 4q13.3 [18] . PPBP (CXCL7) has been was associated with decreased smoking index. The CC
identified as a biomarker in lung cancer [20] . Bdeir et al. genotype and С allele of IL4 (rs2070874) were detected
demonstrated the role of CXCL7 to the pathogenesis of as component of gene-gene combination associated with
acute lung injury [38] . Information about the relationship COPD risk in smokers and non-smokers. The IL4 gene
between COPD and PPBP (CXCL7) is limited. is located at chromosome 5q31.1 together with IL3, IL5,

Volume 1 Issue 1 (2022) 10 https://doi.org/10.36922/gtm.v1i1.91