SERPINE1 rs6092 Variant Is Related to Plasma Coagulation Proteins in Patients with Severe COVID-19 from a Tertiary Care Hospital.

An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (P-Selectin, D-dimer, P-selectin glycoprotein ligand-1, tissue plasminogen activator [tPA], plasminogen activator inhibitor-1, and Factor IX) were assessed by cytometric bead arrays in one- and two-time determinations. Accordingly, SERPINE1 rs6092, P-Selectin (GG 385 pg/mL vs. AG+AA 632 pg/mL, p = 0.0037), and tPA (GG 1858 pg/mL vs. AG+AA 2546 pg/mL, p = 0.0284) levels were different. Patients carrying the CT F5-rs6025 genotype exhibited lower levels of factor IX (CC 17,136 pg/mL vs. CT 10,247 pg/mL, p = 0.0355). Coagulation proteins were also different among IMV patients than non-IMV. PSGL-1 levels were significantly increased in the late stage of COVID-19 (>10 days). The frequencies of F5 rs6025 and SERPINE1 rs6092 variants were not different among IMV and non-IMV. The SERPINE1 rs6092 variant is related to the impaired coagulation process in patients with COVID-19 severe.

The SNP rs13147758 in the HHIP Gene Is Associated With COPD Susceptibility, Serum, and Sputum Protein Levels in Smokers.

BACKGROUND: Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers. MATERIALS AND METHODS: Association analysis was performed by carrying out a case-control study in Mexican mestizo smokers comprised of two groups: tobacco-smoking subjects with COPD (COPD-TS, n = 222) and smokers without COPD (SWOC, n = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene. Allele discrimination was accomplished by qPCR using TaqMan probes, and determination of protein levels in the serum and sputum supernatants (SS) was performed using ELISA. RESULTS: Statistically significant differences were observed in the rs13147758 GG genotype (adjusted p = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (p = 6.6E-06, OR = 2.65) in the case-control comparison. HHIP protein levels were elevated in SS samples from the COPD-TS group compared to those from the SWOC group (p = 0.03). Based on genotype analysis, HHIP protein levels were lower in the serum samples of rs13147758 GG genotype carriers in the COPD-TS group than in the serum samples of rs13147758 GG genotype carriers from the SWOC group (p < 0.05), but there were no differences in the sputum samples. CONCLUSION: The rs13147758 GG genotype and the rs13147758-rs1828591 GA haplotype are associated with susceptibility to COPD. Furthermore, an association in protein levels was observed between the HHIP rs13147758 genotype and COPD in Mexican mestizo smokers.

Participation of HHIP Gene Variants in COPD Susceptibility, Lung Function, and Serum and Sputum Protein Levels in Women Exposed to Biomass-Burning Smoke.

BACKGROUND: A variety of organic materials (biomass) are burned for cooking and heating purposes in poorly ventilated houses; smoke from biomass combustion is considered an environmental risk factor for chronic obstructive pulmonary disease COPD. In this study, we attempted to determine the participation of single-nucleotide variants in the HHIP (hedgehog-interacting protein) gene in lung function, HHIP serum levels, and HHIP sputum supernatant levels in Mexican women with and without COPD who were exposed to biomass-burning smoke. METHODS: In a case-control study (COPD-BS, n = 186, BBES, n = 557) in Mexican women, three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene were analyzed by qPCR; serum and supernatant sputum protein levels were determined through ELISA. RESULTS: The rs13118928 GG genotype is associated with decreased risk (p = 0.021, OR = 0.51, CI95% = 0.27-0.97) and the recessive genetic model (p = 0.0023); the rs1828591-rs13118928 GG haplotype is also associated with decreased risk (p = 0.04, OR = 0.65, CI95% 0.43-0.98). By the dominant model (rs13118928), the subjects with one or two copies of the minor allele (G) exhibited higher protein levels. Additionally, two correlations with the AG genotype were identified: BBES with FEV1 (p = 0.03, r2 = 0.53) and COPD-BS with FEV1/FVC (p = 0.012, r2 = 0.54). CONCLUSIONS: Single-nucleotide variants in the HHIP gene are associated with decreased COPD risk, higher HHIP serum levels, and better lung function in Mexican women exposed to biomass burning.