Comparative analysis of SNPs associated with COVID-19 and chronic liver disease identifies DPP9 as a candidate genetic marker for Long COVID
Introduction
Long COVID is a multisystemic condition characterized by persistent symptoms after acute SARS-CoV-2 infection, whose biological mechanisms are not yet fully understood. Host genetic factors may be associated, and the sharing of genetic architecture with other chronic diseases such as viral hepatitis B and C may aid in understanding this disease.
Methodology
A cross-sectional study was conducted including 150 individuals stratified into two groups: (i) Long COVID and (ii) chronic viral hepatitis B and C. Eighteen single nucleotide polymorphisms (SNPs) previously associated with COVID-19 severity and inflammatory pathways were genotyped using TaqMan® real-time PCR assays.
The analyses of genetic association models were performed using multivariate logistic regression adjusted for gender, self-reported skin color, and comorbidities. Mental health scales for assessing depression (Beck), anxiety (Hamilton), fatigue, and post-COVID functional scale were used both to define the syndrome and for subsequent analyses of the genotypic profile probably associated with Long COVID.
Results
Among all the SNPs analyzed, rs12610495 (A/G) in the DPP9 gene was the only variant consistently associated with Long COVID.
After adjustment for sex, self-reported skin color, and hepatitis status, carriers of the G variant allele demonstrated increased odds of Long COVID under the dominant model (OR = 2.66; 95% CI: 1.08–6.57; p = 0.029) and the overdominant model (OR = 2.96; 95% CI: 1.17–7.52; p = 0.018). The association was more pronounced in women (OR = 3.30; 95% CI: 1.08–10.07).
Exploratory analyses of mental and functional outcomes did not reach statistical significance, although a higher frequency of functional limitation and fatigue was observed among carriers of the G allele.
Conclusion
This study suggests that DPP9 rs12610495 is associated with Long COVID, previously associated only with severe acute COVID, demonstrating that individuals carrying the rs12610495 G variant allele had higher odds of developing Long COVID.
The inclusion of viral hepatitis as a chronic inflammatory condition for comparison contributed to the identification of shared genetic archetypal among diseases, revealing the possible role of DPP9 with Long COVID and highlighting this gene as a relevant target for future validation studies.
Web | DOI | PDF | BMC Infectious Diseases | Open Access
da Silva, Lucas Lima; Maya-Miles, Douglas; Maul, Juliana Cardoso; Paulo, Iolanda Raquel Ferreira; Lewis-Ximenez, Lia Laura; Ivantes, Claudia Alexandra Pontes; Pollo Flores, Priscila; de Paula, Vanessa Salete; Romero-Gómez, Manuel; Villar, Livia Melo
Introduction
Long COVID is a multisystemic condition characterized by persistent symptoms after acute SARS-CoV-2 infection, whose biological mechanisms are not yet fully understood. Host genetic factors may be associated, and the sharing of genetic architecture with other chronic diseases such as viral hepatitis B and C may aid in understanding this disease.
Methodology
A cross-sectional study was conducted including 150 individuals stratified into two groups: (i) Long COVID and (ii) chronic viral hepatitis B and C. Eighteen single nucleotide polymorphisms (SNPs) previously associated with COVID-19 severity and inflammatory pathways were genotyped using TaqMan® real-time PCR assays.
The analyses of genetic association models were performed using multivariate logistic regression adjusted for gender, self-reported skin color, and comorbidities. Mental health scales for assessing depression (Beck), anxiety (Hamilton), fatigue, and post-COVID functional scale were used both to define the syndrome and for subsequent analyses of the genotypic profile probably associated with Long COVID.
Results
Among all the SNPs analyzed, rs12610495 (A/G) in the DPP9 gene was the only variant consistently associated with Long COVID.
After adjustment for sex, self-reported skin color, and hepatitis status, carriers of the G variant allele demonstrated increased odds of Long COVID under the dominant model (OR = 2.66; 95% CI: 1.08–6.57; p = 0.029) and the overdominant model (OR = 2.96; 95% CI: 1.17–7.52; p = 0.018). The association was more pronounced in women (OR = 3.30; 95% CI: 1.08–10.07).
Exploratory analyses of mental and functional outcomes did not reach statistical significance, although a higher frequency of functional limitation and fatigue was observed among carriers of the G allele.
Conclusion
This study suggests that DPP9 rs12610495 is associated with Long COVID, previously associated only with severe acute COVID, demonstrating that individuals carrying the rs12610495 G variant allele had higher odds of developing Long COVID.
The inclusion of viral hepatitis as a chronic inflammatory condition for comparison contributed to the identification of shared genetic archetypal among diseases, revealing the possible role of DPP9 with Long COVID and highlighting this gene as a relevant target for future validation studies.
Web | DOI | PDF | BMC Infectious Diseases | Open Access
