AUTHOR=Liu Tianyu , Yang Lei , Lv Xiaolong , Zuo Chunjian , Jia Chenhao , Yang Zelin , Fan Chongqi , Chen Huanwen 

TITLE=Cumulative evidence for associations between genetic variants in interleukin 17 family gene and risk of human diseases

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1008184

DOI=10.3389/fimmu.2022.1008184

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Genetic association studies have elucidated the link of variants in the interleukin 17 (<italic>IL-17</italic>) family genes with susceptibility to human diseases, yet have obtained controversial outcomes. Therefore, we sought to update comprehensive synopsis of variants in the <italic>IL-17</italic> family genes with susceptibility to human diseases.</p></sec><sec><title>Methods</title><p>Our study screened the Pubmed and Web of Science to enroll eligible articles and performed a meta-analysis, then graded the cumulative evidence of significant association using Venice criteria and false-positive report probability test, and finally assessed the function of variants with strong evidence.</p></sec><sec><title>Results</title><p>Seven variants in <italic>IL-17</italic> family genes had significant relationships with susceptibility to 18 human diseases identified by meta-analyses. Strong evidence was assigned to 4 variants (<italic>IL-17A</italic> rs2275913, <italic>IL-17A</italic> rs8193037, <italic>IL-17F</italic> rs1889570, <italic>IL-17F</italic> rs763780) with susceptibility to 6 human diseases (lung and cervical cancer, spondyloarthritis, asthma, multiple sclerosis, rheumatoid arthritis), moderate to 2 variants with risk of 5 diseases, weak to 5 variants with risk of 10 diseases. Bioinformatics analysis suggested that the variants with strong evidence might fall in putative functional regions. Additionally, positive relationships for 5 variants with risk of 4 diseases (based on two datasets) and 14 variants with risk of 21 diseases (based on one dataset) were considered noteworthy.</p></sec><sec><title>Conclusions</title><p>This study offers updated and comprehensive clues that variants in the <italic>IL-17</italic> family genes are significantly linked with susceptibility to cervical, lung cancer, asthma, multiple sclerosis, rheumatoid arthritis and spondyloarthritis, and elucidates the crucial role of the <italic>IL-17</italic> regions in the genetic predisposition to cancer or noncancerous diseases.</p></sec>