Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population

Takenori Mikami, Akira Meguro, Takeshi Teshigawara, Masaki Takeuchi, Riyo Uemoto, Tatsukata Kawagoe, Eiichi Nomura, Yuri Asukata, Misaki Ishioka, Miki Iwasaki, Kazumi Fukagawa, Kenji Konomi, Jun Shimazaki, Teruo Nishida, Nobuhisa Mizuki, Takenori Mikami, Akira Meguro, Takeshi Teshigawara, Masaki Takeuchi, Riyo Uemoto, Tatsukata Kawagoe, Eiichi Nomura, Yuri Asukata, Misaki Ishioka, Miki Iwasaki, Kazumi Fukagawa, Kenji Konomi, Jun Shimazaki, Teruo Nishida, Nobuhisa Mizuki

Abstract

Purpose: 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.

Figures

Figure 1
Figure 1
Linkage disequilibrium plot of three interleukin 1 alpha to interleukin 1 beta single nucleotide polymorphisms in 559 study participants. The D’ value and r2 value (in parentheses) corresponding to each single nucleotide polymorphism (SNP) pair are expressed as a percentage and shown within the respective square. Red represents a high-pairwise D' value.

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