Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
AuthorsMurphy, Ciara N.; orcid: 0000-0001-6996-7250; email: email@example.com
Walker, Susan P.; email: firstname.lastname@example.org
MacDonald, Teresa M.; email: email@example.com
Keenan, Emerson; orcid: 0000-0003-1966-2293; email: firstname.lastname@example.org
Hannan, Natalie J.; email: email@example.com
Wlodek, Mary E.; orcid: 0000-0002-8490-9099; email: firstname.lastname@example.org
Myers, Jenny; email: Jenny.Myers@manchester.ac.uk
Briffa, Jessica F.; email: email@example.com
Romano, Tania; orcid: 0000-0002-8581-2256; email: firstname.lastname@example.org
Roddy Mitchell, Alexandra; email: email@example.com
Whigham, Carole-Anne; email: firstname.lastname@example.org
Cannon, Ping; email: email@example.com
Nguyen, Tuong-Vi; email: firstname.lastname@example.org
Kandel, Manju; orcid: 0000-0003-1317-5232; email: email@example.com
Pritchard, Natasha; orcid: 0000-0002-7388-2193; email: firstname.lastname@example.org
Tong, Stephen; email: email@example.com
Kaitu’u-Lino, Tu’uhevaha J.; email: firstname.lastname@example.org
MetadataShow full item record
AbstractBiomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency.
CitationInternational Journal of Molecular Sciences, volume 22, issue 14, page e7467
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-07-08, pub-electronic 2021-07-12
Publication status: Published
Showing items related by title, author, creator and subject.
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database StudyDominguez-Valentin, Mev; orcid: 0000-0001-7856-0057; email: Mev.Dominguez.Valentin@rr-research.no; Plazzer, John-Paul; orcid: 0000-0001-5114-4301; email: email@example.com; Sampson, Julian R.; email: Sampson@cardiff.ac.uk; Engel, Christoph; orcid: 0000-0002-7247-282X; email: firstname.lastname@example.org; Aretz, Stefan; orcid: 0000-0002-5228-1890; email: email@example.com; Jenkins, Mark A.; email: firstname.lastname@example.org; Sunde, Lone; email: email@example.com; Bernstein, Inge; email: firstname.lastname@example.org; Capella, Gabriel; orcid: 0000-0002-4669-7320; email: email@example.com; Balaguer, Francesc; orcid: 0000-0002-0206-0539; email: firstname.lastname@example.org; et al. (MDPI, 2021-06-28)Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?Park, JooYong; email: email@example.com; Choi, Ji-Yeob; email: firstname.lastname@example.org; Choi, Jaesung; email: email@example.com; Chung, Seokang; email: firstname.lastname@example.org; Song, Nan; orcid: 0000-0002-9182-1060; email: email@example.com; Park, Sue K.; orcid: 0000-0001-5002-9707; email: firstname.lastname@example.org; Han, Wonshik; email: email@example.com; Noh, Dong-Young; email: firstname.lastname@example.org; Ahn, Sei-Hyun; email: email@example.com; Lee, Jong Won; email: firstname.lastname@example.org; et al. (MDPI, 2021-05-14)In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing CountriesGodman, Brian; orcid: 0000-0001-6539-6972; email: email@example.com; Egwuenu, Abiodun; orcid: 0000-0002-9369-4771; email: firstname.lastname@example.org; Haque, Mainul; orcid: 0000-0002-6124-7993; email: email@example.com; Malande, Oliver Ombeva; email: firstname.lastname@example.org; Schellack, Natalie; email: email@example.com; Kumar, Santosh; orcid: 0000-0002-5117-7872; email: firstname.lastname@example.org; Saleem, Zikria; orcid: 0000-0003-3202-6347; email: email@example.com; Sneddon, Jacqueline; email: firstname.lastname@example.org; Hoxha, Iris; email: email@example.com; Islam, Salequl; email: firstname.lastname@example.org; et al. (MDPI, 2021-06-07)Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.