DEFB1 5'UTR polymorphisms modulate the risk of HIV-1 infection in Mexican women.

Immunologic and genetic factors are involved in HIV-1/AIDS pathogenesis. Defensins are key molecules in innate immunity that participate in the control and/or development of infection and disease. Using PCR-RFLPs, we determined the association between HIV-1/AIDS and human β-defensin 1 (DEFB1) 5'UTR -52 G/A (rs1799946), -44 C/G (rs1800972), and -20 G/A (rs11362) polymorphisms in three groups of women from the state of Sinaloa, located in the Northwest region of Mexico: i) healthy blood donors; ii) sex-workers; and iii) HIV-1 patients. The -52GG genotype was more frequent in blood donors than in patients (p= 0.023; Odds Ratio, OR= 0.49; 95% CI= 0.25-0.95), whereas the - 52GA genotype was significantly higher in patients (p= 0.013; OR= 2.03; 95% CI= 1.11-3.79, statistical power SP= 98.8%), as well as the frequencies of -20A allele (p= 0.017; OR= 1.60; 95% CI= 1.06-2.40), -20AA genotype (p= 0.047; OR = 2.02; 95% CI= 0.93-4.33) and the ACA haplotype with respect to healthy blood donors (p= 0.000012; OR= 5.82; 95% CI= 2.33-16.43, SP= 99.89%) and sex-workers (p= 0.019; OR= 2.18; 95% CI= 1.07-4.46). Conversely, the ACG haplotype was higher in healthy blood donors than in patients (p= 0.009; OR= 0.55; 95% CI= 0.34-0.89). In addition, the -44CC genotype was associated with a low plasma viral load (p= 0.015), whereas AGA, AGG and GGA haplotypes were more prevalent in individuals with high CD4 counts (p= 0.004, 0.046, and 0.029, respectively). These findings associate DEFB1 5'UTR polymorphisms with HIV-1/AIDS in Mexican women for the first time.

[1]  A. Fauci,et al.  The immunopathogenesis of HIV infection. , 1989, Advances in immunology.

[2]  Piero Carninci,et al.  A fast method for high-quality genomic DNA extraction from whole human blood. , 1991, BioTechniques.

[3]  John W. Ward,et al.  1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. , 1993, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[4]  J J Goedert,et al.  Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. , 1997, Science.

[5]  Ji Ming Wang,et al.  β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6 , 1999 .

[6]  G. K. Johnson,et al.  Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands. , 1999, Infection and immunity.

[7]  R. Kaul,et al.  How important is the 'quality' of the cytotoxic T lymphocyte (CTL) response in protection against HIV infection? , 2001, Immunology letters.

[8]  L. Kwak,et al.  Mammalian defensins in immunity: more than just microbicidal. , 2002, Trends in immunology.

[9]  R. Jurevic,et al.  Single-nucleotide polymorphisms and haplotype analysis in beta-defensin genes in different ethnic populations. , 2002, Genetic testing.

[10]  A. Haase,et al.  Transmission, acute HIV-1 infection and the quest for strategies to prevent infection , 2003, Nature Medicine.

[11]  Yun Feng,et al.  Mycobacterium bovis bacille Calmette-Guérin (BCG) enhances human beta-defensin-1 gene transcription in human pulmonary gland epithelial cells. , 2003, Acta pharmacologica Sinica.

[12]  A. Amoroso,et al.  A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children , 2004, AIDS.

[13]  R. Blumenthal,et al.  Human β-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection , 2005, Journal of Virology.

[14]  F. Marshall,et al.  Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. , 2006, Cancer research.

[15]  Yong-yong Shi,et al.  SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci , 2023, Cell Research.

[16]  G. Wong,et al.  Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children , 2006, Genes and Immunity.

[17]  M. Boniotto,et al.  DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children , 2006, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[18]  N. Anthonisen,et al.  Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study , 2006, Respiratory research.

[19]  S. Crovella,et al.  DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children , 2006, AIDS.

[20]  S. Crovella,et al.  Transcriptional effect of DEFB1 gene 5' untranslated region polymorphisms. , 2007, Cancer research.

[21]  F. Cardinale,et al.  Association of β-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis , 2008, Genes and Immunity.

[22]  L. Palombi,et al.  Single-nucleotide polymorphisms in human β-defensin-1 gene in Mozambican HIV-1-infected women and correlation with virologic parameters , 2008, AIDS.

[23]  M. Lederman,et al.  Increased levels of human beta-defensins mRNA in sexually HIV-1 exposed but uninfected individuals. , 2008, Current HIV research.

[24]  H. Rangel-Villalobos,et al.  Genetic data of 15 autosomal STRs (Identifiler kit) of three Mexican Mestizo population samples from the States of Jalisco (West), Puebla (Center), and Yucatan (Southeast). , 2009, Forensic science international. Genetics.

[25]  R. Presland,et al.  Association of a genetic polymorphism (-44 C/G SNP) in the human DEFB1 gene with expression and inducibility of multiple β-defensins in gingival keratinocytes , 2009, BMC oral health.

[26]  C. Giaquinto,et al.  Role of β-Defensin-1 Polymorphisms in Mother-to-Child Transmission of HIV-1 , 2009, Journal of acquired immune deficiency syndromes.

[27]  A. Abbas,et al.  Association of beta-defensin 1 single nucleotide polymorphism with atopic dermatitis. , 2009, The Egyptian journal of immunology.

[28]  J. S. Velarde-Félix,et al.  SNP 668C (-44) alters a NF-kappaB1 putative binding site in non-coding strand of human beta-defensin 1 (DEFB1) and is associated with lepromatous leprosy. , 2009, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[29]  E. Prado-Montes de Oca,et al.  Human beta-defensin 1: a restless warrior against allergies, infections and cancer. , 2010, The international journal of biochemistry & cell biology.

[30]  A. Vieira,et al.  The Antimicrobial Peptide DEFB1 Is Associated with Caries , 2010, Journal of dental research.

[31]  C. Trevisiol,et al.  Beta defensin‐1 gene (DEFB1) polymorphisms are not associated with atopic dermatitis in children and adolescents from northeast Brazil (Recife, Pernambuco) , 2010, International journal of dermatology.

[32]  J. Turpin,et al.  Outcomes of a National Institute of Allergy and Infectious Diseases Workshop on understanding HIV-exposed but seronegative individuals. , 2011, AIDS research and human retroviruses.

[33]  S. Crovella,et al.  DEFB1 gene 5' untranslated region (UTR) polymorphisms in inflammatory bowel diseases. , 2012, Clinics.

[34]  K. Gianesin,et al.  Cross-talk between virus and host innate immunity in pediatric HIV-1 infection and disease progression. , 2012, The new microbiologica.

[35]  E. Donadi,et al.  Functional single-nucleotide polymorphisms in the DEFB1 gene are associated with systemic lupus erythematosus in Southern Brazilians , 2012, Lupus.

[36]  D. Nurjadi,et al.  Impaired β-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage. , 2013, The Journal of infectious diseases.

[37]  J. A. Estrada-Aguirre,et al.  Protective effect of CCR5 Delta-32 allele against HIV-1 in Mexican women. , 2013, Current HIV research.

[38]  E. Prado Montes de Oca,et al.  Polymorphism in cathelicidin gene (CAMP) that alters Hypoxia‐inducible factor (HIF‐1α::ARNT) binding is not associated with tuberculosis , 2014, International journal of immunogenetics.

[39]  Kamran Ghaedi,et al.  Defensins: Antimicrobial Peptides of Innate Immunity , 2014 .