title: Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome.
abstract: BACKGROUND
  Nephrotic syndrome (NS) is a debilitating renal problem in children resulting from an interaction between environmental and genetic factors including human leukocyte antigen genes (HLA). The aim of this work was to study the probable link between HLA alleles/haplotypes and NS in south India.
  
  
  METHODS
  HLA DRB1*/DQB1* alleles were genotyped in 183 NS (76 steroid sensitive-SSNS; 107 steroid resistant-SRNS) and paediatric healthy controls (PHCs; n = 91) using polymerase chain reaction-sequence specific primers (PCR-SSP). HLA-A/-B genotyping was performed for patients (n = 70) positive for DRB1*07-DQB1*02 haplotype to identify four locus extended haplotype.
  
  
  RESULTS
  The following alleles and haplotypes were strongly associated with NS (P < 0.05 as significant): DRB1*07 (SSNS, P < 7.98 × 10(-6) ; SRNS, P < 0.008), DQB1*02 (SSNS, P < 3.99 × 10(-6) ; SRNS, P < 0.002), DRB1*07-DQB1*02 (SSNS, P < 1.32 × 10(-4) ; SRNS, P < 0.010), DRB1*07-DQB1*0301,0304 (DQ7) (SSNS, P < 0.001) and DRB1*03-DQB1*02 (SRNS, P < 0.048). Protective associations were observed for alleles DRB1*10 (SRNS, P < 0.013), DQB1*05 (SSNS, P < 4.34 × 10(-6) ; SRNS, P < 0.01), DQB1*06 (SSNS, P < 0.003), and haplotypes DRB1*10-DQB1*06 (SSNS, P < 0.046; SRNS, P < 0.032) and DRB1*15-DQB1*05 (SSNS, P < 0.018). HLA-A/-B typing of 70 NS cases with two locus haplotype DRB1*07-DQB1*02 (70/183; 38.25%) revealed the presence of an extended haplotype 'A*03-B*07-DRB1*07-DQB1*02' (n = 35; 50%).
  
  
  CONCLUSIONS
  Our study revealed strong susceptible association of DRB1*07 with SRNS and DQB1*02 with SSNS. A gender predominant protective association was observed for DRB1*10 with SRNS females; DQB1*05 with SSNS and SRNS males. Further, the study documented the presence of an extended haplotype and pleiotropic action of DRB1*/DQB1* alleles in immune-mediated aetiology of NS in south India.
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health & Hospital for Children, Madras Medical College, Chennai, Tamil Nadu, India.
authors.forename: Aravind Selvin Kumar
authors.initials: AS
authors.lastname: Ramanathan
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health & Hospital for Children, Madras Medical College, Chennai, Tamil Nadu, India.|Department of Pediatric Nephrology, Dr. Mehta's Children's Hospital, Chennai, Tamil Nadu, India.
authors.forename: Prabha
authors.initials: P
authors.lastname: Senguttuvan
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
authors.forename: Rathika
authors.initials: R
authors.lastname: Chinniah
authors.affiliation: Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Murali
authors.initials: M
authors.lastname: Vijayan
authors.affiliation: Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Thirunavukkarasu
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
authors.forename: Kamaraj
authors.initials: K
authors.lastname: Raju
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
authors.forename: Dhivakar
authors.initials: D
authors.lastname: Mani
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
authors.forename: Padma Malini
authors.initials: PM
authors.lastname: Ravi
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health & Hospital for Children, Madras Medical College, Chennai, Tamil Nadu, India.
authors.forename: Padmaraj
authors.initials: P
authors.lastname: Rajendran
authors.affiliation: Health City, Narayana Hospital, Bangalore, India.
authors.forename: Jeyaram Illiayaraja
authors.initials: JI
authors.lastname: Krishnan
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Karuppiah
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005938:Glucocorticoids / Q000627:therapeutic use; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D009402:Nephrosis, Lipoid / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D005938:Glucocorticoids; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C456920:HLA-DRB1*07 antigen; D011239:Prednisolone
keywords: Extended haplotype; focal segmental glomerulosclerosis; human leukocyte antigen; nephrotic syndrome; south Indian children; steroid resistant nephrotic syndrome