Significant association found between the rs1205 T-Dom genotype and risk of COVID-19 death or hospitalization among American Indians

By Dr. Sanchari Sinha Dutta, Ph.D.Aug 14 2023Reviewed by Benedette Cuffari, M.Sc.

In a recent study posted to the medRxiv preprint server, researchers identify an association between the C-reactive protein (CRP) gene variant rs1205 and coronavirus disease 2019 (COVID-19) severity.

Study: Genetic Variant rs1205 is Associated with COVID-19 Outcomes: The Strong Heart Study and Strong Heart Family Study. Image Credit: peterschreiber.media / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

The COVID-19 pandemic, which was caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe damage to both economic and healthcare sectors. To date, the World Health Organization (WHO) reports that COVID-19 has been responsible for over 768 million infections and 6.9 million deaths.

Age, socioeconomic status, and the presence of comorbidities are major risk factors for COVID-19 morbidity and mortality. Race/ethnicity has also been correlated with disease severity throughout the pandemic.

In this context, previous studies indicate that, as compared to those of White ethnicity, American Indian and Alaskan Native populations have 2.5- and 2.1-fold greater risks for COVID-19-related hospitalization and death, respectively. Certain genetic risk factors might be responsible for higher disease severity in ethnic minorities.

In the current study, scientists investigate possible associations between CRP gene variants and COVID-19 severity among American Indian Tribal communities.

Study design

The current study utilized datasets obtained from the Strong Heart Study (SHS) and allied Strong Heart Family Study (SHFS). Both SHS and SHFS are the largest ongoing epidemiological studies involving American Indians from 12 different Tribal communities located in Arizona, North, and South Dakotas, as well as Oklahoma.

Genetic datasets and medical records related to cardiovascular disease incidence and risk factors, including COVID-19, were analyzed to identify possible genetic risk factors associated with COVID-19 hospitalization and mortality. The study was conducted between January 2020 and January 2023.

Previously reported candidate variants associated with COVID-19 pathogenesis and clinical outcomes were selected. A total of 21 candidate variants including genes in the interferon (IFN) response pathway, apolipoprotein E (APOE), transmembrane protease, serine 2 (TMPRSS2), toll-like receptor 3 (TLR3), human leukocyte antigen (HLA) complex, and the ABO blood group were selected for the final analysis.

Among the 3,780 participants from the SHS and SHFS cohorts, genotypic data, as well as COVID-19 hospitalization and mortality data from 91 individuals, were identified and included in the study analysis.

Important observations

Among the 21 candidate gene variants analyzed in the study, the rs1205 T allele-dominant (T-Dom) genotype was significantly associated with COVID-19 hospitalization and mortality. This association remained unaltered after adjusting for the study participants’ age, sex, body mass index (BMI), history of cardiovascular disease, as well as genetic relatedness. Moreover, this association became more significant among the younger participants within the SHFS cohort.

The rs1205 variant is a C/T single nucleotide polymorphism in the 3' untranslated region of the CRP gene.  Pre-existing evidence on rs1205 variant has highlighted its ability to alter serum levels of CRP, which is an important component of the innate immune system.

Several studies have also reported associations of CRP variants with infectious diseases and vaccine outcomes. Taken together, these findings confirm the association of CRP gene and its variant rs1205 with COVID-19 pathogenesis and severity.

Individuals with the rs1205 T allele-dominant genotype exhibited lower serum levels of CRP as compared to those who were homozygous for the C allele. Although high CRP levels are directly related to COVID-19 severity, the lower level of an innate immune factor like CRP in the early phase of viral exposure could lead to increased morbidity. Previous studies have also indicated that CRP genotypes associated with lower CRP levels can increase the severity of infectious diseases.

Study significance

The current study identifies a statistically significant association between the rs1205 T allele-dominant genotype and COVID-19-related hospitalization and mortality among American Indian Tribal communities. This genotype appears to be associated with lower serum levels of CRP, which is an important component of the innate immune system.

Identifying common genetic variants in high-risk populations is important for developing novel therapeutic and preventive interventions to combat COVID-19. Thus, more studies are needed to identify other genetic variants of the CRP gene in other high-risk populations.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.