title: MDR1 3435T and 1236T alleles delay disease progression to pediatric AIDS but have no effect on HIV-1 vertical transmission.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in the MDR1 gene, coding for the drug transporter P-glycoprotein, may modulate the response to antiretroviral therapy and susceptibility to HIV-1 infection. We investigated whether the MDR1 SNPs C1236T (exon 12) and C3435T (exon 26) affect HIV-1 vertical transmission and progression to pediatric AIDS.
  
  
  METHODS
  The MDR1 genotypes were identified by PCR-restriction fragment length polymorphism (RFLP) assays in 219 HIV-infected, 128 exposed uninfected children and 231 HIV-seronegative blood donors. Genotype and haplotype frequencies were estimated in the different groups. The median follow-up time of the infected cohort was 108 months and AIDS-free time was evaluated for the different MDR1 genotypes in 171 HIV-infected children.
  
  
  RESULTS
  We found that both C1236T and C3435T polymorphisms were highly frequent in the studied groups (approximately 0.44) and showed strong linkage disequilibrium. There was no association between MDR1 genotypes and HIV-1 vertical transmission. However, a protective effect against progression to AIDS was associated with MDR1 3435CT, 1236CT and 1236TT genotypes (P = 0.005, P = 0.024 and P = 0.026, respectively). Moreover, haplotype pairs' analysis showed that the 3435CT/1236CT and 3435CT/1236TT exerted a significant protection against progression to pediatric AIDS (P = 0.0025 and P = 0.006, respectively).
  
  
  CONCLUSIONS
  We conclude that in Argentinean children, MDR1 genotypes are associated with progression to AIDS, but they do not affect HIV-1 susceptibility by vertical transmission. These results support the notion that P-glycoprotein plays a role in HIV-1 infection independently from its role in drug transport.
authors.affiliation: Laboratorio de Biología Celular y Retrovirus-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
authors.forename: Carolina P
authors.initials: CP
authors.lastname: Bellusci
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rocco
authors.forename: Paula C
authors.initials: PC
authors.lastname: Aulicino
authors.forename: Debora
authors.initials: D
authors.lastname: Mecikovsky
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D000483:Alleles; D001118:Argentina / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1