Gender‐dependent multiple cross‐phenotype association of interferon lambda genetic variants with peripheral blood profiles in healthy individuals

Background Type III interferons (IFN), also called as lambda IFNs (IFN‐λs), are antiviral and immunomodulatory cytokines that are evolutionarily important in humans. Given their central roles in innate immunity, they could be influencing other aspects of human biology. This study aimed to examine th...

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Bibliographic Details
Published in:Molecular genetics & genomic medicine 2024-01, Vol.12 (1), p.e2292-n/a
Main Authors: Roy, Debarati Guha, Singh, Lucky, Chaturvedi, Himanshu K., Chinnaswamy, Sreedhar
Format: Article
Language:English
Subjects:
Alleles
Biobanks
Blood
Chronic illnesses
COVID-19
cross‐phenotype association
Cytokines
Demographic variables
Female
Gender
Genes
Genetic diversity
Genetic variance
Genomes
Genomics
Hepatitis C
Humans
IFNL
IFNL3
IFNL4
Immunomodulation
Infections
Innate immunity
Interferon
Interferon Lambda
Interferons - genetics
Interferons - metabolism
Interleukins - genetics
Interleukins - metabolism
Lipoproteins (very low density)
Male
Males
Model testing
Monocytes
Peripheral blood
Phenotype
Phenotypes
PheWAS
Physiology
Regression analysis
rs117648444
rs12979860
rs28416813
rs368234815
rs4803217
Thyroid gland
Triglycerides
Tropical diseases
Uric Acid
Viral infections
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Summary:Background Type III interferons (IFN), also called as lambda IFNs (IFN‐λs), are antiviral and immunomodulatory cytokines that are evolutionarily important in humans. Given their central roles in innate immunity, they could be influencing other aspects of human biology. This study aimed to examine the association of genetic variants that control the expression and/or activity of IFN‐λ3 and IFN‐λ4 with multiple phenotypes in blood profiles of healthy individuals. Methods In a cohort of about 550 self‐declared healthy individuals, after applying several exclusion criteria to determine their health status, we measured 30 blood parameters, including cellular, biochemical, and metabolic profiles. We genotyped them at rs12979860 and rs28416813 using competitive allele‐specific PCR assays and tested their association with the blood profiles under dominant and recessive models for the minor allele. IFN‐λ4 variants rs368234815 and rs117648444 were also genotyped or inferred. Results We saw no association in the combined cohort under either of the models for any of the phenotypes. When we stratified the cohort based on gender, we saw a significant association only in males with monocyte (p = 1 × 10−3) and SGOT (p = 7 × 10−3) levels under the dominant model and with uric acid levels (p = 0.01) under the recessive model. When we tested the IFN‐λ4 activity modifying variant within groupings based on absence or presence of one or two copies of IFN‐λ4 and on different activity levels of IFN‐λ4, we found significant (p 
ISSN:2324-9269
2324-9269
DOI:10.1002/mgg3.2292