title: Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population.
abstract: OBJECTIVE
  Polymorphisms in the interleukin 1 alpha (IL1A) and IL1B gene regions were previously associated with keratoconus in a Korean population. In the present study, we investigated whether the IL1A and IL1B polymorphisms are associated with keratoconus in a Japanese population.
  
  
  METHODS
  A total of 169 Japanese patients with keratoconus and 390 Japanese healthy controls were recruited. We genotyped one IL1A single nucleotide polymorphism (SNP; rs2071376) and two IL1B SNPs (rs1143627 and rs16944) to compare the frequencies of alleles, genotypes, and haplotypes between cases and controls.
  
  
  RESULTS
  Statistically significant association was observed for rs1143627 (-31 T>C) in the IL1B promoter region; the T allele of rs1143627 was associated with an increased risk of keratoconus (p=0.014, corrected p value [pc]=0.043, odds ratio=1.38). The C allele of rs16944 (-511 C>T) in the IL1B promoter region had a 1.33-fold increased risk of keratoconus, although this increase did not reach statistical significance (p=0.033, pc=0.098). The TT genotype of rs1143627 was weakly associated with an increased risk of keratoconus (p=0.033, pc=0.099, odds ratio=1.52). However, no significant differences were found in the allele and genotype frequencies between the cases and controls for rs2071376 in IL1A. Regarding haplotypic diversity, the haplotype created by the T allele of rs1143627 and C allele of rs16944 was associated with a 1.72-fold increased risk of keratoconus (p=4.0×10(-5), pc=1.6×10(-4)).
  
  
  CONCLUSIONS
  Our results replicate associations reported recently in a Korean population. Thus, IL1B may play an important role in the development of keratoconus through genetic polymorphisms.
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Mikami
authors.forename: Akira
authors.initials: A
authors.lastname: Meguro
authors.forename: Takeshi
authors.initials: T
authors.lastname: Teshigawara
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Riyo
authors.initials: R
authors.lastname: Uemoto
authors.forename: Tatsukata
authors.initials: T
authors.lastname: Kawagoe
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nomura
authors.forename: Yuri
authors.initials: Y
authors.lastname: Asukata
authors.forename: Misaki
authors.initials: M
authors.lastname: Ishioka
authors.forename: Miki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fukagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Konomi
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007564:Japan; D007640:Keratoconus / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: C508585:IL1B protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta