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A deeper understanding of genetic variations can provide new insights into the biological mechanisms underlying the occurrence and development of immunodeficiency syndrome (AIDS). By utilizing multiple bioinformatic analyses and functional annotations, we identified single-nucleotide polymorphisms (SNPs) in the NLR signaling pathway that may affect HIV-1 infection and AIDS progression. Then, a case\u2013control study was performed to screen risk-related variants by genotyping candidate SNPs in a sample of 500 men who have sex with men (MSM) with HIV-1 and 500 healthy controls from the Han population in Northern China. The results revealed significant association between five SNPs (NLRP3 rs4612666, MAVS rs17857295, MAVS rs6084497, MAVS rs16989000, and JAK1 rs4244165) and HIV-1 infection. Interestingly, the gene\u2013gene interaction model composed of five SNPs exhibited a cumulative effect on the disease. Specially, the increase in risk alleles carried by the samples elevated the risk of contracting HIV-1. In addition, three SNPs (IL1B rs1143623, STAT1 rs1467199 and STAT1 rs2066804) were associated with CD4+ T cell counts in patients with AIDS. Three SNPs (OAS1 rs1131454, NLRP3 rs10754558, and MAVS rs867335) were found to be related to the clinical staging of AIDS. This finding provides insights into the genetic variants in NLR signaling pathway genes in HIV-1 infection and AIDS progression among MSM in Northern China.<\/jats:p>","DOI":"10.3390\/ijms26083484","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:32:53Z","timestamp":1744169573000},"page":"3484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Variants in the NOD-like Receptor Signaling Pathway Are Associated with HIV-1\/AIDS in a Northern Chinese Population"],"prefix":"10.3390","volume":"26","author":[{"given":"Tingyu","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of 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