Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes.

To determine whether genetic predisposition to endometriosis varies depending on ethnicity and in association with expression quantitative trait loci (eQTL) in a Taiwanese population. We conducted a genome-wide association study (GWAS) and replicated it in 259 individuals with laparoscopy-confirmed stage III or IV endometriosis (cases) and 171 women without endometriosis (controls). Their genomic DNA was extracted from blood and evaluated by the GWAS of Taiwan Biobank Array. Novel genetic variants that predispose individuals to endometriosis were identified using GWAS and replication, including rs10739199 (P = 6.75 × 10-5) and rs2025392 (P = 8.01 × 10-5) at chromosome 9, rs1998998 (P = 6.5 × 10-6) at chromosome 14, and rs6576560 (P = 9.7 × 10-6) at chromosome 15. After imputation, strong signals were exhibited by rs10822312 (P = 1.80 × 10-7) at chromosome 10, rs58991632 (P = 1.92 × 10-6) and rs2273422 (P = 2.42 × 10-6) at chromosome 20, and rs12566078 (P = 2.5 × 10-6) at chromosome 1. We used the Genotype-Tissue Expression (GTEx) database to observe eQTL. Among these SNPs, the cis-eQTL rs13126673 of inturned planar cell polarity protein (INTU) showed significant association with INTU expression (P = 5.1 × 10-33). Moreover, the eQTL analysis was performed on endometriotic tissues from women with endometriosis. The expression of INTU in 78 endometriotic tissue of women with endometriosis is associated with rs13126673 genotype (P = 0.034). To our knowledge, this is the first GWAS to link endometriosis and eQTL in a Taiwanese population.

Killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C) allorecognition patterns in women with endometriosis.

Endometriosis shares similarities with several autoimmune diseases. The human leukocyte antigen (HLA)-C genotype is associated with several human autoimmune diseases. HLA-C is a ligand of killer cell immunoglobulin receptors (KIRs) and is an essential regulator of natural killer cell activity, which is associated with endometriosis progression. Polymorphisms in HLA-C and KIR affect the activity of NK cells and susceptibility to several diseases. Therefore, we attempted to investigate an association between HLA-C genotype and KIR polymorphism and the occurrence of endometriosis. We tested the association of certain KIR and HLA-C combinations and the development of endometriosis by characterizing both KIR and HLA-C genes in 147 women with endometriosis and 117 controls. The HLA-C genotypes and KIR polymorphisms were analyzed via DNA-based method for higher-resolution genotyping. We found that the occurrence of HLA-C*03:03*01 was increased in endometriosis than in control groups. Analysis of various KIR haplotypes revealed differences between the endometriosis and control cohorts. The number of KIR centromeric A/A haplotypes was increased in the endometriosis group than controls. Moreover, the endometriosis cohort was characterized by reduced number of KIR2DS2-positive individuals in the Han Chinese population. Our current findings suggest that the KIR and HLA-C genotypes are associated with the pathogenesis of endometriosis.

Pelvic endometriosis with peritoneal fluid reduces pregnancy rates in women undergoing intrauterine insemination.

OBJECTIVE: This study investigated the occurrence of peritoneal fluid in women undergoing intrauterine insemination (IUI) and its correlation with the stage of pelvic endometriosis and its influence on pregnancy outcomes. MATERIALS AND METHODS: A retrospective case-control design was used to recruit 272 infertile women with pelvic endometriosis. The treatment protocol consisted of controlled ovarian hyperstimulation with downregulation and gonadotropin for IUI treatment following ultrasound and laparoscopic intervention. The amount and color of the peritoneal fluid were determined during laparoscopy. RESULTS: The mean amount of peritoneal fluid with pelvic endometriosis that was detected using transvaginal ultrasound was ~ 15.1 mL. Women whose cycles contained more peritoneal fluid had significantly lower pregnancy rates (17.2% and 31.3%, respectively). The total clinical pregnancy rate was not significantly different between the two groups with reddish and yellowish peritoneal fluid who had pelvic endometriosis. CONCLUSION: Pelvic endometriosis and peritoneal fluid, detected through vaginal ultrasound, have negative effects on the pregnancy outcome of IUI treatment.

Successful management of aortic dissection in a patient with Marfan syndrome during pregnancy.

The antenatal diagnosis of aortic dissection carries a grave prognosis. Although cases of pregnant women with Marfan syndrome have been encountered that resulted either in sudden death or emergency surgery at diagnosis, cesarean section delivery for patients who survive is associated with the risk of anesthesia and manipulation of the abdomen. Such complications can be avoided if the aortic dissection can be treated conservatively. We report the successful treatment of an aortic dissection with pharmacologic therapy and the birth of a healthy infant.

Matrix remodeling and endometriosis.

The physiological changes in endometriosis involving multiple steps of matrix remodeling include abnormal tissue growth, invasion, and adhesion formation. Endometriosis-associated abnormal matrix remodeling is affected by several molecular factors including proteolytic enzymes and their inhibitors, which mediate tissue turnover throughout the reproductive tract to maintain the integrity of the endometrium, and ovarian steroids, which normally regulate reconstruction and breakdown of endometrium in the menstrual cycle. In addition, various growth factors, such as platelet-derived growth factor, transform growth factor ß, and epidermal growth factor, direct modulation of growth, activation, and chemotaxis which may facilitate endometrial cell adhesion onto the peritoneal mesothelium during the development of endometriosis. Furthermore, cell adhesion molecules are believed to be critically involved in most cellular-level processes including cellular differentiation, motility, and attachment with the extracellular matrix. The present review focuses on the abnormal matrix remodeling process and its possible regulatory mechanism in association with endometriosis development. As a greater understanding of the cause of endometriosis is achieved, better treatment of the disease and its prevention become possible. (Reprod Med Biol 2005; 4: 93-99).