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Emanuel syndrome is a rare autosomal disorder characterized by microcephaly, heart defects, cleft palate and developmental delay. However, there is a lack of specific prenatal screening for Emanuel syndrome. To screen for early diagnostic marker genes in fetuses with karyotype+der[22]t(11;22)(q23;q11) of Emanuel syndrome. Transcriptome sequencing and clinical trait data of t(11;22)(q23;q11) translocation samples were screened from the GEO database. The differentially expressed genes (DEGs) were screened by principal component analysis of gene expression by R package, and intersections were taken with balanced and unbalanced DEGs. Then, the correlation with clinical traits was determined by WGCNA analysis, GO and KEGG enrichment analysis, and then univariate Cox analysis and Lasso analysis were performed to obtain the key genes. The core regulatory genes were obtained after protein-protein interaction (PPI) network analysis. A total of 50 DEGs were obtained after differential analysis. WGCNA analysis showed that DEG was associated with the chromosomal imbalance and age module. GO and KEGG enrichment analyses showed candidate genes were associated with exocytic vesicle membrane, synaptic vesicle membranes, glycoprotein complex, dystrophin-associated glycoprotein complex and malaria. COX and Lasso analyses yielded 5 hub genes, including ZBED9, RGS20, SGCB, ETV5, and ZAP70. The results of PPI identified the key regulatory gene associated with chromosomal imbalance as the ZAP70 gene. ZAP70 may be a key gene for early diagnosis of Emanuel syndrome in fetuses with+der[22]t(11;22)(q23;q11) karyotype.
RESUMO
INTRODUCTION: The correlation between sex hormone levels and pelvic bone mineral density in people with urinary incontinence (UI) has not been evaluated. This study explored the association between sex hormones, pelvic bone mineral density, and UI, and analyzed the association between pelvic bone mineral density-combined sex hormones and UI in women. METHOD: The data of the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were used in this cross-sectional study. Women aged 20 years and older with complete sex steroid hormone and pelvic bone mineral density data were included. Outcomes were stress UI (SUI), urgency UI (UUI), and mixed UI (MUI). Sex steroid hormone included testosterone, estradiol, and sex hormone binding globulin (SHBG). Multivariate logistic regression analyses with the odds ratios (ORs) and 95% confidence intervals (CIs) were used. RESULTS: Of 2,442 women, 579 had SUI, 202 had UUI, and 344 had MUI. The estimated multiplicative interactions were significantly between testosterone and pelvic bone mineral density, between SHBG and pelvic bone mineral density on UI (p = 0.002, p = 0.003), MUI (p = 0.036, p < 0.001), and SUI (p = 0.008, p = 0.044), respectively. High pelvic bone mineral density was associated with UI (p = 0.022) and MUI (p = 0.028) in the age <45-year-old subgroup. Multiplicative interactions were between testosterone and pelvic bone mineral density on all types of UI in the age <45-year-old subgroup, on SUI in women who did not have vaginal deliveries, and on UI in women who had more than one-time vaginal delivery. CONCLUSION: Our study found negatively multiplicative interactions between testosterone, SHBG, and pelvic bone mineral density on UI, MUI, and SUI. Similar results were found in women aged <45 years old and in women who had more than one-time vaginal delivery. Clinicians may consider testosterone or SHBG supplementation and pelvic density enhancement in women with SUI, MUI, and low endogenous testosterone levels.
