title: Polymorphisms in IL-1 gene cluster and its association with the risk of perinatal HIV transmission, in an Indian cohort.
abstract: Host genetic diversity plays a very important role in protecting infants exposed to HIV-1 through their mothers. IL-1 family genes are key mediators of inflammatory responses and no studies are available on its association with perinatal HIV transmission. We aimed to evaluate if single nucleotide polymorphisms in IL-1 family genes are associated with perinatal HIV transmission. Infants of HIV positive women were genotyped for five polymorphic loci in IL1 gene cluster namely; IL1R1 (rs2234650), IL1A (rs1800587), IL1B (rs16944), IL1B (rs1143634), and IL1RN (rs315952) using polymerase chain reaction with sequence specific primers (PCR-SSP) method. Haplotype block structure was determined using Haploview and statistical analysis was done using PyPop. In this cohort based observational study significantly increased frequency of CT genotype in IL1R1 (rs2234650) was observed in positive vs. negative children (76.4% vs. 42.2%, p = 0.023), while CC genotype was significantly (p = 0.022) high in exposed uninfected children compared to infected ones (51.1% vs. 17.6%). These significances, however, did not stand the Bonferroni corrections. Haplotypic analysis demonstrated that the TCCCT haplotype was significantly associated (p = 0.002) with HIV transmission and remained significant even after Bonferroni correction. The children who had the protective CC genotype at IL1R1 (rs2234650) and were still positive had the TTC haplotype for IL1A (rs1800587):IL1B (rs1143634):IL1R1 (rs2234650). In contrast, 16 out of 19 (84.2%) children who had the CT genotype and were still negative had the protective CTC haplotype for IL1A (rs1800587):IL1B (rs16944):IL1B (rs1143634). IL1R1 (rs2234650) polymorphisms CT/CC along the specific haplotypes of the IL-1 gene family can be exploited as possible markers for prediction of perinatal HIV transmission.
authors.affiliation: Department of Infectious Diseases Biology, National Institute for Research in Reproductive Health (DHR/ICMR), J. M. Street, Parel, Mumbai 400 012, Maharashtra, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Ahir
authors.forename: Deepali
authors.initials: D
authors.lastname: Chaudhari
authors.forename: Vijay
authors.initials: V
authors.lastname: Chavan
authors.forename: Padmaja
authors.initials: P
authors.lastname: Samant-Mavani
authors.forename: Ruchi
authors.initials: R
authors.lastname: Nanavati
authors.forename: Preeti
authors.initials: P
authors.lastname: Mehta
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mania-Pramanik
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D019562:Viral Load
chemical_list: D005819:Genetic Markers; D007375:Interleukin-1; D017472:Receptors, Interleukin-1
keywords: Cytokine genes; IL-1 family; Perinatal HIV; SNPs