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- Plaza-Florido, A., et al.
(författare)
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Distinct whole-blood transcriptome profile of children with metabolic healthy overweight/obesity compared to metabolic unhealthy overweight/obesity
- 2020
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. Methods: Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5’-end RNA-sequencing. Results: Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions. Conclusions: The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity. Impact: A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype.The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2.The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.
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- Aghajanova, Lusine, et al.
(författare)
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No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility
- 2015
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:1, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?SUMMARY ANSWER: We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.WHAT IS KNOWN ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).MAIN RESULTS AND THE ROLE OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.LIMITATIONS, REASONS FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.WIDER IMPLICATIONS OF THE FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.STUDY FUNDING/COMPETING INTERESTS: This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.
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- Altmäe, Signe, et al.
(författare)
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Guidelines for the design, analysis and interpretation of 'omics' data : focus on human endometrium
- 2013
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 20:1, s. 12-28
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.
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- Laanpere, M, et al.
(författare)
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Folate-metabolizing gene variants and pregnancy outcome of IVF
- 2011
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Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 22:6, s. 603-614
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence that folate status and variation in folate-metabolizing genes are involved in female reproductive functions. This study evaluated the influence of maternal blood folate, vitamin B(12), homocysteine and 10 folate pathway gene variants on IVF outcome. Also, the prevalence of these polymorphisms was compared in 439 female IVF patients and 225 fertile controls. MTHFR 677 CT heterozygotes had a higher proportion of good-quality embryos and an increased chance of pregnancy. MTHFR 1793 GA heterozygosity was associated with a lower percentage of previously failed IVF treatments. Heterozygosity for FOLR1 1816 C/delC and 1841 G/A was associated with a raised risk of pregnancy loss. The CTH 1208 GT genotype was associated with an increased chance of pregnancy and a smaller number of previously failed IVF cycles and the genotype frequency was lower in IVF patients with three or more previously failed IVF treatments compared with fertile controls. SLC19A1 80 GA heterozygotes had a decreased number of previously failed IVF treatments and were more prevalent among fertile controls. In conclusion, polymorphisms in folate-metabolizing genes may affect ovarian stimulation and pregnancy outcome of IVF, and heterozygous individuals, rather than the wild-type homozygotes, appeared to have more favourable outcomes.
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| 7. |
- Murto, Tiina, et al.
(författare)
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Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
- 2014
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 28:6, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- Folic acid supplements are commonly used by infertile women and lead to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.
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