Abstract
BackgroundVariation in host genetic factors may result in variation in the host immune response to the infection. Some chronic diseases may also affect individuals’ susceptibility to infectious diseases. The aim of this study was to evaluate the association of the host genetic factors mostly involved in inflammation, as well as hypercholesterolemia and diabetes with mild flu in an Iranian population.MethodsIn this cross-sectional study, nasopharyngeal swab samples were collected from 93 patients referred to primary care centers of Markazi, Semnan, and Zanjan provinces (central Iran) due to flu-like symptoms between March 2015 and December 2018. Of these, PCR test identified 49 influenza A/H1N1 and 44 flu-negative individuals. Twelve single-nucleotide polymorphisms (SNPs) in RPAIN, FCGR2A, MBL-2, CD55, C1QBP, IL-10, TNF-α and an unknown gene were genotyped using iPLEX GOLD SNP genotyping analysis. Hypercholesterolemia and diabetes status was determined based on the physician diagnosis. Association of the host genetic variants, hypercholesterolemia and diabetes with mild A/H1N1 flu was assessed with univariable and multivariable logistic regression analysis as implemented in Stata software (v.14). Statistical tests were considered as significant at 0.05 levels.ResultsFrequency of diabetes and hypercholesterolemia, as well as participants mean age was significantly higher in the flu-negative rather than the flu-positive group. Of 12 SNPs, nine did not show any significant association with mild flu in our study (rs1801274, rs1800451, rs2564978, rs361525, rs1800450, rs1800871, rs1800872, rs1800896, rs1800629). Possessing G vs. A allele in two SNPs (rs3786054 and rs8070740) was associated with a threefold increase in the chance of mild flu when compared to flu-negative patients (95% CI: 1.1, 22.0). Possessing C allele (vs. A) in the rs9856661 locus also increased the chance of mild flu up to 2 folds (95% CI: 1.0, 10.0).ConclusionThe results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1QBP and RPAIN genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient’s age, BMI, diabetes, and hypercholesterolemia. Complementary functional genomic studies would shed more light on the underlying mechanism of human immunity associated with these genetic markers. The identified genetic factors may have the same role in susceptibility to similar respiratory infections with RNA viruses, like SARS, MERS and COVID-19. Future genetic association studies targeting these RNA viruses, especially COVID-19 is recommended. Studies on other ethnic groups would also shed light on possible ethnic variations in genetic susceptibility to respiratory RNA viruses.Trial registry IR.PII.REC.1399.063
Highlights
Variation in host genetic factors may result in variation in the host immune response to the infection
We examined a wide range of human genetic variants in different genes involved in immune response against viral infection in order to explore their potential association with mild influenza in human
The results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1q binding protein (C1QBP) and replication protein A interacting protein (RPAIN) genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient’s age, BMI, diabetes, and hypercholesterolemia
Summary
Variation in host genetic factors may result in variation in the host immune response to the infection. New strains cause the epidemics among humans and animals These viruses use the host cell system for their replication and propagation and affect host cell signaling pathways [2]. The severity of the disease is usually associated with the host factors such as age (over 65 years), pregnancy, obesity and underlying diseases including lung, cardiovascular, renal or hepatic disease, chronic metabolic disorders (including diabetes) or immunodeficiency diseases [7]. Underlying diseases such as diabetes and hypercholesterolemia are associated with the highest risk and the most common contributing factors [8,9,10]. A key point for the studies of host innate immunity factors is the observation of increased mortality among young adults and children without pre-identified risk factors [12]
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