Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nat Genet. 2010 Aug;42(8):707-10. doi: 10.1038/ng.612. Epub 2010 Jul 4.
Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.
虽然子宫内膜异位症的发病机制尚不清楚，但遗传因素被认为在其发病机制中起着关键作用。通过全基因组关联研究和一项共纳入 1907 名日本子宫内膜异位症患者（病例）和 5292 名对照的复制研究，我们发现 rs10965235（P=5.57x10(-12)，优势比=1.44）与子宫内膜异位症显著相关，该 SNP 位于 9p21 染色体上的 CDKN2BAS 基因中，编码细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA。通过精细定位，发现与该 SNP 关联最强的 SNP 位于 CDKN2BAS 基因的内含子 16 中，可能参与调节 p15、p16 和 p14 的表达。位于 1p36 染色体上的 WNT4 所在的 LD 块中的 SNP rs16826658 也可能与子宫内膜异位症有关（P=1.66x10(-6)，优势比=1.20），WNT4 被认为在女性生殖道的发育中起着重要作用。我们的研究结果表明，这些区域是子宫内膜异位症的新易感位点。
