Genetic variants in SCGB1A1 affect sputum CC16 levels in wood smoke COPD and are associated with COPD susceptibility in smokers

<b>Introduction:</b> The CC16 protein has been proposed as a potential biomarker in COPD secondary to smoking; however, no studies on smoke exposure from biomass burning. Furthermore, it is unknown whether genetic variants in <i>SCGB1A1</i>, the gene encoding CC16, modify protein levels. We aimed to identify SNPs in <i>SCGB1A1</i> associated with COPD (smoking and exposure to biomass burning smoke) and correlate them with serum and sputum CC16 levels. <b>Methods:</b> Genetic association analysis in Mexican mestizo cases and controls, divided into 4 groups: smokers with COPD (COPD-S, n= 263), smokers without COPD (SWOC, n= 486), exposed to smoke from biomass burning with COPD (COPD-BBS, n = 180), exposed to smoke from biomass burning without COPD (EBBS, n= 532). We evaluated three SNPs (rs906902, rs10836312, and rs3741240) in <i>SCGB1A1</i>. Allelic discrimination was performed by qPCR and CC16 levels by ELISA.&nbsp;Statistical analyzes with RStudio v1.3.1073, Epi Info v7.0, Epidat v3.1, Haploview v4.2, and PLINK v1.07. <b>Results:</b> In both comparisons, smokers and biomass burning exposed subjects, the GC and AT haplotypes (rs906902-rs10836312) were associated with a higher COPD risk (smokers: p= 1.11E-02, OR= 1.96; p= 3.60E-0.3, OR= 2.56; exposed: (p=1.65E-09, OR=2.98, p=1.36E-16, OR=4.35). The CC16 levels were higher in COPD smokers with TT genotype vs. CT (p= 0.04). CC16 was correlated with lower FVC in COPD-S, COPD-BBS, and EBBS. <b>Conclusions:</b> The rs10836312 affects CC16 levels, and a negative correlation was found between FVC and CC16 levels in EBBS carriers of the TT genotype of rs10836312 and exposed with and without COPD carriers of the GG genotype of rs3741240 in sputum samples.