Abstract
Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10−5; odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41–2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10−7; OR, 1.90; 95% CI, 1.49–2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.
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Acknowledgements
All women with endometriosis were registered at the Niigata University Hospital, the Nagasaki University Hospital, the Kumamoto University Hospital, the Takarazuka City Hospital, the National Hospital Organization Kyoto Medical Center, the Nagaoka Red Cross Hospital, the Kido Hospital, the Niigata Cancer Center Hospital, the Suibarago Hospital, the Joetsu General hospital, the Kaetsu Hospital, the Niigata Medical Center, the Muikamachi Hospital, the Toyama Red Cross Hospital and the Syonai Hospital. We thank China Seki, Akemi Yukawa, Yumiko Sato and Junko Kitayama for their technical assistance.
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Hata, Y., Nakaoka, H., Yoshihara, K. et al. A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population. J Hum Genet 58, 517–520 (2013). https://doi.org/10.1038/jhg.2013.32
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DOI: https://doi.org/10.1038/jhg.2013.32
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