{"doi":"10.1111/iji.12646","title":"<i>CCR5</i> promoter region polymorphisms in systemic lupus erythematosus","abstract":"<jats:title>Abstract</jats:title><jats:p>This study investigated the impacts of <jats:italic>CCR5</jats:italic> promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing <jats:italic>CCR5</jats:italic> genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European‐derived and 93 African‐derived) and 375 controls (243 European‐derived and 132 African‐derived) were genotyped for the CCR2‐64I G &gt; A (rs1799864), CCR5‐59353 C &gt; T (rs1799988), CCR5‐59356 C &gt; T (rs41469351), CCR5‐59402 A &gt; G (rs1800023) and CCR5‐59653 C &gt; T (rs1800024) polymorphisms through polymerase chain reaction‐restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the <jats:italic>CCR5</jats:italic> haplotypes and as a possible confounding factor in the binary logistic regression. European‐derived patients showed a higher frequency of CCR5 wild‐type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [<jats:italic>p</jats:italic> = .003 (OR 3.5, 95%CI 1.6–7.5) and 2.0% vs. 7.2% (residual <jats:italic>p</jats:italic> = 2.9E − 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African‐derived patients and controls [10% vs. 20.5% (residual <jats:italic>p</jats:italic> = .003), 29.4% vs. 17.4% (residual <jats:italic>p</jats:italic> = .003) and 3.9% vs. 0.8% (residual <jats:italic>p</jats:italic> = .023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African‐derived group and when all patients were grouped for comparison [<jats:italic>p</jats:italic><jats:sub>corrected</jats:sub> = .012 (OR 3.0; 95%CI 3.0–333.3) and <jats:italic>p</jats:italic><jats:sub>corrected</jats:sub> = .0006 (OR 6.8; 95%CI 1.9–24.8), respectively]. In conclusion, this study indicates that <jats:italic>CCR5</jats:italic> promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European‐derived patients and as a susceptibility factor for class IV nephritis in African‐derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African‐derived patients, which could modify the CCR5 protein expression in specific cell subsets.</jats:p>","journal":"International Journal of Immunogenetics","year":2024,"id":647683,"datarank":0.2186899858169861,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.010745831649002483,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.010745831649002483,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1687581,"name":"Amanda Henrique de Oliveira","orcid":"0000-0002-1733-2840","position":1,"is_corresponding":false},{"id":329932,"name":"Camila Rosat Consiglio","orcid":"0000-0002-8901-2328","position":2,"is_corresponding":false},{"id":851091,"name":"Odirlei André Monticielo","orcid":"0000-0003-0720-2097","position":3,"is_corresponding":false},{"id":905857,"name":"Ricardo Machado Xavier","orcid":"0000-0001-6570-4533","position":4,"is_corresponding":false},{"id":875885,"name":"Natália Schneider","orcid":"0000-0003-1950-4391","position":5,"is_corresponding":false},{"id":1687586,"name":"Joel Henrique Ellwanger","orcid":"0000-0002-1040-2738","position":6,"is_corresponding":false},{"id":1677532,"name":"José Artur Bogo Chies","orcid":"0000-0001-7025-0660","position":7,"is_corresponding":false},{"id":1687580,"name":"Juliana da Silveira Schauren","orcid":"0000-0002-1920-1369","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>CCR5</i> promoter region polymorphisms in systemic lupus erythematosus","abstract":"<jats:title>Abstract</jats:title><jats:p>This study investigated the impacts of <jats:italic>CCR5</jats:italic> promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing <jats:italic>CCR5</jats:italic> genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European‐derived and 93 African‐derived) and 375 controls (243 European‐derived and 132 African‐derived) were genotyped for the CCR2‐64I G &gt; A (rs1799864), CCR5‐59353 C &gt; T (rs1799988), CCR5‐59356 C &gt; T (rs41469351), CCR5‐59402 A &gt; G (rs1800023) and CCR5‐59653 C &gt; T (rs1800024) polymorphisms through polymerase chain reaction‐restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the <jats:italic>CCR5</jats:italic> haplotypes and as a possible confounding factor in the binary logistic regression. European‐derived patients showed a higher frequency of CCR5 wild‐type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [<jats:italic>p</jats:italic> = .003 (OR 3.5, 95%CI 1.6–7.5) and 2.0% vs. 7.2% (residual <jats:italic>p</jats:italic> = 2.9E − 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African‐derived patients and controls [10% vs. 20.5% (residual <jats:italic>p</jats:italic> = .003), 29.4% vs. 17.4% (residual <jats:italic>p</jats:italic> = .003) and 3.9% vs. 0.8% (residual <jats:italic>p</jats:italic> = .023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African‐derived group and when all patients were grouped for comparison [<jats:italic>p</jats:italic><jats:sub>corrected</jats:sub> = .012 (OR 3.0; 95%CI 3.0–333.3) and <jats:italic>p</jats:italic><jats:sub>corrected</jats:sub> = .0006 (OR 6.8; 95%CI 1.9–24.8), respectively]. In conclusion, this study indicates that <jats:italic>CCR5</jats:italic> promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European‐derived patients and as a susceptibility factor for class IV nephritis in African‐derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African‐derived patients, which could modify the CCR5 protein expression in specific cell subsets.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37984413","pmcid":null,"openalex_id":"https://openalex.org/W4388852184","authors":[],"funders":[{"funder_name":"Coordenação de Aperfeiçoamento de Pessoal de Nível Superior","grant_id":"","title":null},{"funder_name":"Conselho Nacional de Desenvolvimento Científico e Tecnológico","grant_id":"","title":null},{"funder_name":"Coordenação de Aperfeiçoamento de Pessoal de Nível Superior","grant_id":"","title":null},{"funder_name":"Conselho Nacional de Desenvolvimento Científico e Tecnológico","grant_id":"","title":null}],"total_grants":4,"fwci":0.38,"citation_percentile":0.63163191,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/iji.12646","host_type":"publisher"},{"url":"https://doi.org/10.1111/iji.12646","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37984413","host_type":"repository"}],"fields_of_study":["Systemic Lupus Erythematosus Research","T-cell and B-cell Immunology","Chemokine receptors and signaling","Humans","Genetic Predisposition to Disease","Lupus Erythematosus, Systemic","Polymorphism, Genetic","Genotype","Nephritis","Receptors, CCR5","Promoter Regions, Genetic","Gene Frequency","Polymorphism, Single Nucleotide"],"mesh_terms":["Gene Frequency","Genotype","Humans","Lupus Erythematosus, Systemic","Nephritis","Polymorphism, Genetic","Promoter Regions, Genetic","Receptors, CCR5","Genetic Predisposition to Disease","Polymorphism, Single Nucleotide"],"keywords":["Haplotype","Genotype","Internal medicine","Immunology","Allele frequency","Allele","Case-control study","Lupus nephritis","Biology","Gastroenterology","Genetics","Medicine","Disease","Gene","Inflammation","systemic lupus erythematosus","immunogenetics","Brazilian Population","Rs333","Ccr5 Promoter Polymorphisms"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T01:44:14.844278Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}