Variants of FOXO3 and RPA3 genes affecting IGF-1 levels alter the risk of development of primary osteoarthritis

2021 ◽  
Vol 184 (1) ◽  
pp. 29-39
Author(s):  
I C M Pelsma ◽  
K M J A Claessen ◽  
P E Slagboom ◽  
D van Heemst ◽  
A M Pereira ◽  
...  
Keyword(s):  
Potential Role ◽  
High Growth ◽  
Estimating Equation ◽  
Knee Oa ◽  
Primary Osteoarthritis ◽  
Minor Alleles ◽  
Male Patients ◽  
Male Carriers ◽  
Female Carriers

Introduction Pathologically high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in patients with acromegaly are associated with arthropathy. Several studies highlight the potential role of the GH/IGF-1 axis in primary osteoarthritis (OA). We aimed to disentangle the role of IGF-1 levels in primary OA pathogenesis. Methods Patients from the Genetics osteoARthritis and Progression (GARP) Study with familial, generalized, symptomatic OA (n = 337, mean age: 59.8 ± 7.4 years, 82% female) were compared to Leiden Longevity Study (LLS) controls (n = 456, mean age: 59.8 ± 6.8 years, 51% female). Subjects were clinically and radiographically assessed, serum IGF-1 levels were measured, and 10 quantitative trait loci (QTL) in the FOXO3, IGFBP3/TNS3, RPA3, SPOCK2 genes, previously related to serum IGF-1 levels, were genotyped. Linear or binary logistic generalized estimating equation models were performed. Results Serum IGF-1 levels were increased in OA patients, with male patients exhibiting the strongest effect (males OR = 1.10 (1.04–1.17), P=0.002 vs females OR = 1.04 (1.01–1.07), P = 0.02). Independent of the increased IGF-1 levels, male carriers of the minor allele of FOXO3 QTL rs4946936 had a lower risk to develop hip OA (OR = 0.41 (0.18–0.90), P = 0.026). Additionally, independent of IGF-1 levels, female carriers of the minor alleles of RPA3 QTL rs11769597 had a higher risk to develop knee OA (OR = 1.90 (1.20–2.99), P = 0.006). Conclusion Patients with primary OA had significantly higher IGF-1 levels compared to controls. Moreover, SNPs in the FOXO3 and RPA3 genes were associated with an altered risk of OA. Therefore, altered IGF-1 levels affect the development of OA, and are potentially the result of the pathophysiological OA process.

scholarly journals Potential role of circulating microRNAs (486-5p, 497, 509-5p and 605) in metabolic syndrome Egyptian male patients

2019 ◽  
Vol Volume 12 ◽  
pp. 601-611 ◽  
Author(s):  
Mohamed Bakr Zaki ◽  
Ahmed Ibrahim Abulsoud ◽  
Ahmed Mohamed Elsisi ◽  
Ahmed Soliman Doghish ◽  
Ossama Abd Elmotaal Mansour ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Potential Role ◽  
Circulating Micrornas ◽  
Male Patients

scholarly journals Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study

2020 ◽  
Author(s):  
Qiang Liu ◽  
James R. Hebert ◽  
Nitin Shivappa ◽  
Jianjun Guo ◽  
Ke Tao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Estimating Equation ◽  
Mediation Analyses ◽  
Knee Oa ◽  
Inflammatory Index ◽  
Symptomatic Knee ◽  
Osteoarthritis Initiative ◽  
Reduce Risk

Abstract Background To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest. Methods In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DIITM) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident: (1) radiographic knee OA (ROA) (i.e., a KL grade ≥2), (2) symptomatic knee OA (SxOA) (i.e., a combination of a frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess potential mediation by BMI in the DII-OA relation. Results Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI): 1.15 to 2.62, Ptrend= 0.007). The corresponding OR for SxOA was 1.43 (95% CI: 1.16 to 1.76, Ptrend = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI: 1.04,1.13) for ROA and 1.13 (95% CI: 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of total effect, respectively. Conclusions A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting inflammatory potential of diet may be beneficial to reduce risk of knee OA.

Gender-related differences in the oxidant state of cells in Fanconi anemia heterozygotes

2011 ◽  
Vol 392 (7) ◽  
Author(s):  
Sandra Petrovic ◽  
Andreja Leskovac ◽  
Jelena Kotur-Stevuljevic ◽  
Jelena Joksic ◽  
Marija Guc-Scekic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Genetic Disorder ◽  
Significant Difference ◽  
Heterozygous Carriers ◽  
Male Carriers ◽  
Female Carriers

Abstract Fanconi anemia (FA) is a rare cancer-prone genetic disorder characterized by progressive bone marrow failure, chromosomal instability and redox abnormalities. There is much biochemical and genetic data, which strongly suggest that FA cells experience increased oxidative stress. The present study was designed to elucidate if differences in oxidant state exist between control, idiopathic bone marrow failure (idBMF) and FA cells, and to analyze oxidant state of cells in FA heterozygous carriers as well. The results of the present study confirm an in vivo prooxidant state of FA cells and clearly indicate that FA patients can be distinguished from idBMF patients based on the oxidant state of cells. Female carriers of FA mutation also exhibited hallmarks of an in vivo prooxidant state behaving in a similar manner as FA patients. On the other hand, the oxidant state of cells in FA male carriers and idBMF families failed to show any significant difference vs. controls. We demonstrate that the altered oxidant state influences susceptibility of cells to apoptosis in both FA patients and female carriers. The results highlight the need for further research of the possible role of mitochondrial inheritance in the pathogenesis of FA.

scholarly journals Anal screening cytology

CytoJournal ◽  
2005 ◽  
Vol 2 ◽  
pp. 5 ◽  
Author(s):  
Gladwyn Leiman
Keyword(s):  
Potential Role ◽  
Intraepithelial Neoplasia ◽  
New Disease ◽  
Disease Entity ◽  
Anal Lesion ◽  
Screening Programs ◽  
Male Patients ◽  
Morphologic Classification

This issue of CytoJournal contains an article on screening for anal intraepithelial neoplasia in high-risk male patients. This accompanying Editorial focuses on current understanding of this relatively new disease entity, with insights as to the potential role of screening cytopathology in the epidemiology, pathophysiology and clinical management of this HIV and HPV related anal lesion, which predominates in male patients living long-term with AIDS. Mention is made of techniques of obtaining samples, methods of preparation, and morphologic classification. Issues of anoscopic confirmation, as well as topical and surgical management are emphasized. The similarity of initial experiences in anal screening to problems encountered early in cervical cancer screening programs several decades ago, are highlighted.

scholarly journals Inflammatory Potential of Diet and Risk of Incident Knee Osteoarthritis: A Prospective Cohort Study

2020 ◽  
Author(s):  
Qiang Liu ◽  
James R. Hebert ◽  
Nitin Shivappa ◽  
Jianjun Guo ◽  
Ke Tao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Estimating Equation ◽  
Mediation Effect ◽  
Mediation Analyses ◽  
Knee Oa ◽  
Inflammatory Index ◽  
Symptomatic Knee ◽  
Osteoarthritis Initiative

Abstract Background To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest.Methods In the Osteoarthritis Initiative, the Dietary inflammatory index (DII®) was calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident: (1) radiographic knee OA (ROA) (i.e., a KL grade ≥ 2), (2) symptomatic knee OA (SxOA) (i.e., a combination of a frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between DII® scores and incident knee OA. We performed mediation analyses to assess the mediation effect of BMI in the DII-OA relation.Results Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) quartile of DII®, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) quartile of DII® was 1.73 (95% confidence interval (CI): 1.15 to 2.62, P for trend = 0.007). The corresponding OR for SxOA was 1.43 (95% CI: 1.16 to 1.76, P for trend = 0.001). The DII®-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI: 1.04,1.13) for ROA and 1.13 (95% CI: 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of total effect, respectively.Conclusions A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting inflammatory potential of diet may be beneficial to reduce risk of knee OA.

scholarly journals Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Qiang Liu ◽  
James R. Hebert ◽  
Nitin Shivappa ◽  
Jianjun Guo ◽  
Ke Tao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Estimating Equation ◽  
Generalized Estimating Equation ◽  
Mediation Analyses ◽  
Knee Oa ◽  
Inflammatory Index ◽  
Symptomatic Knee ◽  
Osteoarthritis Initiative

Abstract Background To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest. Methods In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DII™) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident (1) radiographic knee OA (ROA) (i.e., a KL grade ≥ 2) and (2) symptomatic knee OA (SxOA) (i.e., a combination of frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess the potential mediation by BMI in the DII-OA relation. Results Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI) 1.15 to 2.62, Ptrend = 0.007). The corresponding OR for SxOA was 1.43 (95% CI 1.16 to 1.76, Ptrend = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI 1.04, 1.13) for ROA and 1.13 (95% CI 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of the total effect, respectively. Conclusions A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting the inflammatory potential of diet may be beneficial to reduce the risk of knee OA.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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