title: A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.
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.
authors: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors: Yuki
authors: Y
authors: Hata
authors: Hirofumi
authors: H
authors: Nakaoka
authors: Kosuke
authors: K
authors: Yoshihara
authors: Sosuke
authors: S
authors: Adachi
authors: Kazufumi
authors: K
authors: Haino
authors: Masayuki
authors: M
authors: Yamaguchi
authors: Nobumichi
authors: N
authors: Nishikawa
authors: Katsunori
authors: K
authors: Kashima
authors: Tetsuro
authors: T
authors: Yahata
authors: Atsushi
authors: A
authors: Tajima
authors: Atsushi
authors: A
authors: Watanabe
authors: Shigeo
authors: S
authors: Akira
authors: Kazuyoshi
authors: K
authors: Hosomichi
authors: Ituro
authors: I
authors: Inoue
authors: Kenichi
authors: K
authors: Tanaka
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D007564:Japan; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: C508584:IL1A protein, human; D053582:Interleukin-1alpha