title: Association of IL1A and IL1B loci with primary open angle glaucoma.
abstract: BACKGROUND
  Recent studies suggest that glaucoma is a neurodegenerative disease in which secondary degenerative losses occur after primary insult by raised Intraocular pressure (IOP) or by other associated factors. It has been reported that polymorphisms in the IL1A and IL1B genes are associated with Primary Open Angle Glaucoma (POAG). The purpose of our study was to investigate the role of these polymorphisms in eastern Indian POAG patients.
  
  
  METHODS
  The study involved 315 unrelated POAG patients, consisting of 116 High Tension Glaucoma (HTG) patients with intra ocular pressure (IOP) > 21 mmHg and 199 non-HTG patients (presenting IOP < 20 mmHg), and 301 healthy controls from eastern India. Genotypes were determined by polymerase chain reaction and restriction digestion for three single nucleotide polymorphisms (SNPs): IL1A (-889C/T; rs1800587), IL1B (-511C/T; rs16944) and IL1B (3953C/T; rs1143634). Haplotype frequency was determined by Haploview 4.1 software. The association of individual SNPs and major haplotypes was evaluated using chi-square statistics. The p-value was corrected for multiple tests by Bonferroni method.
  
  
  RESULTS
  No significant difference was observed in the allele and genotype frequencies for IL1A and IL1B SNPs between total pool of POAG patients and controls. However, on segregating the patient pool to HTG and non-HTG groups, weak association was observed for IL1A polymorphism (-889C/T) where -889C allele was found to portray risk (OR = 1.380; 95% CI = 1.041-1.830; p = 0.025) for non-HTG patients. Similarly, 3953T allele of IL1B polymorphism (+3953C/T) was observed to confer risk to HTG group (OR = 1.561; 95% CI = 1.022-2.385; p = 0.039). On haplotype analysis it was observed that TTC was significantly underrepresented in non-HTG patients (OR = 0.538; 95% CI = 0.356- 0.815; p = 0.003) while TCT haplotype was overrepresented in HTG patients (OR = 1.784; 95% CI = 1.084- 2.937; p = 0.022) compared to control pool. However, after correction for multiple tests by Bonferroni method, an association of only TTC haplotype with non-HTG cases sustained (pcorrected = 0.015) and expected to confer protection.
  
  
  CONCLUSIONS
  The study suggests that the genomic region containing the IL1 gene cluster influences the POAG pathogenesis mostly in non-HTG patients in eastern India. A similar study in additional and larger cohorts of patients in other population groups is necessary to further substantiate the observation.
authors.affiliation: Molecular & Human Genetics Division, Indian Institute of Chemical Biology, Council of Scientific & Industrial Research, Kolkata, India.
authors.forename: Suddhasil
authors.initials: S
authors.lastname: Mookherjee
authors.forename: Deblina
authors.initials: D
authors.lastname: Banerjee
authors.forename: Subhadip
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Antara
authors.initials: A
authors.lastname: Banerjee
authors.forename: Indranil
authors.initials: I
authors.lastname: Mukhopadhyay
authors.forename: Abhijit
authors.initials: A
authors.lastname: Sen
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007194:India; D053582:Interleukin-1alpha / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D007429:Intraocular Pressure / Q000235:genetics / Q000276:immunology; D015810:Linkage Disequilibrium; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta