title: Associations between common variants in the MDR1 (ABCB1) gene and ulcerative colitis among North Indians.
abstract: OBJECTIVE
  There are suggestions that the MDR1 (ABCB1) gene is associated with ulcerative colitis (UC) in Caucasians. We investigated whether common MDR1 variants were associated with UC in the genetically heterogeneous North Indian population.
  
  
  METHODS
  Confirmed cases of UC and healthy controls frequency matched for age (+/-10 years) and geographic region were studied. Three exonic (C1236T, G2677T/A, and C3435T) and one promoter (C129T) single nucleotide polymorphism (SNP) in the gene were assessed. Allelic, genotypic, and haplotypic associations were evaluated.
  
  
  RESULTS
  A total of 270 patients and 274 controls were studied. The mean age at diagnosis (+/-SD) of the patients was 38.6 (+/-12.4) years. Most patients had left-sided disease (63.3%) and steroids were administered to them (78%). All SNPs were in Hardy-Weinberg equilibrium in the controls. SNP C129T was monomorphic in the population. SNP C1236T was significantly (P=0.05) overrepresented in the UC patients. Borderline nonsignificant associations were also evident with SNP G2677A/T. Three-marker (C1236T, G2677T/A, C3435T) and two-marker (C1236T, G2677T/A) haplotype analysis revealed significant associations with UC (TTT, P=0.04; TGT, P=0.01; TT, P=0.01; CT, P=0.03). There were indications that SNPs C1236T and G2677T/A were significantly associated with earlier age of onset (<29 years) of UC and left-sided disease. Specific haplotypes comprising the three SNPs were associated with steroid response.
  
  
  CONCLUSIONS
  Our findings indicate that common SNPs in the MDR1 gene are associated with an overall susceptibility for UC and specific disease phenotypes in North Indians. Larger studies to replicate these findings are required.
authors.affiliation: Department of Genetics, University of Delhi, South Campus, New Delhi, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Juyal
authors.forename: Vandana
authors.initials: V
authors.lastname: Midha
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.forename: Ajit
authors.initials: A
authors.lastname: Sood
authors.forename: Ernest
authors.initials: E
authors.lastname: Seidman
authors.forename: B K
authors.initials: BK
authors.lastname: Thelma
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013256:Steroids / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D013256:Steroids