Non-synonymous WNT16 polymorphisms alleles are associated with different osteoarthritis phenotypes

García-Ibarbia, Carmen; Neila, Sara; Garcés, Carlos; Alonso, Maria Augusta; Zarrabeitia, Marı́a T.; Valero, Carmen; Ortiz, Fernando Rosell; Riancho, José A.

doi:10.1007/s00296-017-3783-5

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…Radiographic OA was associated with high BMD and increased rate of bone loss . WNT16 rs2908004 polymorphism was associated with different OA phenotypes (atrophic or hypertrophic) . Our results indicate WNT16 rs2908004 polymorphism conferred susceptibility to OA by comparing genotype and allele distribution between cases and controls.…”

Section: Discussionmentioning

confidence: 66%

“…We selected five SNPs (DVL1 rs61735963, WNT16 rs2908004, ITIH5 rs10795550, LRP1 rs1799986 and SFRP1 rs1127379) and investigated their association with OA risk in a Chinese population. Two SNPs (WNT16 rs2908004 and LRP1 rs1799986) were reported . WNT16 could influence bone mineral density (BMD), cortical bone thickness and osteoporotic fracture risk .…”

Section: Discussionmentioning

confidence: 99%

“…Two SNPs (WNT16 rs2908004 and LRP1 rs1799986) were reported. 21 72 0.63 (0.42-0.94); 0.022 0.50 (0.31-0.81); 0.005 0.67 (0.45-1.02); 0.060 0.59 (0.40-0.85) .48 (0.27-0.85); 0.012 0.53 (0.32-0.88) bone mineral density (BMD), cortical bone thickness and osteoporotic fracture risk. 23 Radiographic OA was associated with high BMD and increased rate of bone loss.…”

Section: Discussionmentioning

confidence: 99%

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Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Huang

Jiang

Yang

et al. 2019

J Cellular Molecular Medi

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Excessive activation of the Wnt signalling pathway in the articular cartilage is demonstrated to be related to the onset and severity of osteoarthritis (OA). However, few studies have investigated the association between variants in Wnt‐pathway‐related genes and the risk of OA by searching Pubmed and EMBASE. Totally, 471 knee OA patients and 532 controls were recruited from three hospitals to evaluate the associations of five genetic variants (rs61735963, rs2908004, rs10795550, rs1799986 and rs1127379) with the risk of knee OA. These polymorphisms were genotyped through polymerase chain reaction and Sanger sequencing. Genetic risk scores (GRSs) were calculated to evaluate the combined effect of these genetic variants. No significant association was found between OA risk and polymorphisms (rs61735963, rs10795550 or rs1127379). However, WNT16 rs2908004 polymorphism was correlated with a decreased risk of OA, especially among females, smokers, non‐drinkers and individuals with age < 60 years or BMI ≥ 25. This SNP was also associated with Kellgren‐Lawrence grade and CRP. Similarly, LRP1 rs1799986 polymorphism decreased the risk of OA among males, smokers, drinkers and individuals with age < 60 years or BMI ≥ 25. TT genotype was more frequent in the group of VAS ≥ 6 versus VAS < 6. A low GRS was positively correlated with a decreased risk of OA. In addition, rs2908004 or rs1799986 polymorphism reduces the expression of WNT16 or LRP1. In conclusion, two SNPs (rs2908004 and rs1799986) are associated with the decreased risk of OA by regulating the Wnt pathway.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Huang

Jiang

Yang

et al. 2019

J Cellular Molecular Medi

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“…While previous work indicated that there was no association between Wnt16 gene polymorphisms and osteoarthritis (OA) ( 90 ), recently, two SNPs of the Wnt16 gene (rs2707466 and rs2908004) known to be associated with BMD have been implicated in the hip and knee OA phenotypes in Caucasian patients in a sex-dependent manner ( 91 ). This report was the first to suggest the involvement of the Wnt pathway in determining the OA phenotypes.…”

Section: Wnt16 In Osteoarthritis Pathogenesismentioning

confidence: 99%

Wnt16 signaling in bone homeostasis and osteoarthristis

Liu

2022

Front. Endocrinol.

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Wnts are secreted cysteine-rich glycoproteins involved in joint development and skeletal homeostasis and have been implicated in the occurrence of osteoarthritis. Over the past decade, Wnt16, a member of the Wnt family, has received widespread attention for its strong association with bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. In recent years, further studies have shed light on the role of Wnt16 a positive regulator of bone mass and protective regulator of osteoarthritis progression. Transduction mechanisms and crosstalk involving Wnt16 signaling have also been illustrated. More importantly, local Wnt16 treatment has been shown to ease osteoarthritis, inhibit bone resorption, and promote new bone formation in bone defect models. Thus, Wnt16 is now a potential therapeutic target for skeletal diseases and osteoarthritis. This paper reviews our current understanding of the mechanisms by which Wnt16 signaling regulates bone homeostasis and osteoarthritis.

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“…В настоящее время определены генетические факторы, которые играют важную роль в патогенезе различных остеоартрозов, например: пол (остеоартритом чаще страдают женщины); наследственная артроофтальмопатия (синдром Стиклера, при котором имеется мутация гена COL2A1, или гена COL11A2); различные наследственные патологические состояния и/или заболевания суставов и костей (гипермобильный синдром, различные дисплазии и др. ); этниче-ская принадлежность пациентов [2,8,15], однако изучение влияния генетических факторов в развитии вторичных остеоартрозов (диспластический, ревматоидный, подагрический) единичны и практически отсутствуют при идиопатическом коксартрозе [5,12], что и явилось целью нашей работы.…”

Section: генетические аспекты развития коксартрозаunclassified

Effect of IL4-589C>T, FCGR2A-166His>Arg, DEFB1-20G>A, DEFB1-52G>A gene polymorphisms on TNFα, IL-1β, IL-4, and IL-10 contents in the patients with primary hip osteoarthrosis

2020

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Our objective was to study the effects of IL4-589C>T, FCGR2A-166His>Arg, DEFB1-20G>A, DEFB1-52G>A gene polymorphisms upon content of TNFα, IL-1β, IL-4, and IL-10 in primary osteoarthrosis of the hip joints. We performed a survey of 100 patients of Russian ethnicity (average age 61.3±8.5 years) with primary coxarthrosis at the stage III-IV who lived in the Trans-Baikal region. The control group (n = 100), were local residents, comparable by age (60±8.3 years), gender, habitation place and nationality. The exclusion criteria were as follows: close relationship; other types of osteoarthritis (post-traumatic, rheumatoid, metabolic, etc.); dysplastic syndromes and phenotypes; acute and chronic inflammatory diseases at the exacerbation stage; diabetes mellitus; osteoporosis; vascular diseases; obesity; malignant neoplasia; alcohol abuse. Along with clinical examination, the following laboratory methods were applied: immunological techniques, i.e., determination of TNFα, IL-1β, IL-4, IL-10; genetic testing using polymerase chain reaction, e.g., a point mutation of the IL4 gene at the 589(C>T) position, FCGR2A at 166(His>Arg) site, DEFB1 at the 20(G>A) and 52(G>A) positions. DNA from the peripheral blood of patients was used for the molecular genetic analysis. Radiographic examination was also carried out. The data were statistically processed using STATISTICA 6.1 software package (StatSoft, USA), Microsoft Office Excel 2019 for Windows 10. The differences were considered statistically significant at p ≤ 0.05. Results. The -589T/T genotype of IL4-589C>T gene polymorphism indirectly contributes to higher content of TNFα and IL-1β for primary osteoarthritis of the hip joints. The patients with -166Arg/Arg genotype have a 1.3-fold increase of certain cytokine concentrations, e.g., TNFα and IL-1β, as compared with -166His/Arg genotype, and, conversely, lower content of IL-4 and IL-10 (1.3- fold) in comparison with -166His/His genotype. The patients with -20A/A genotype showed higher levels of TNFα and IL-1β, respectively, 1.2 and 1.3 times, compared with -20G/G genotype, and 1.3 times versus the -20G/A genotype. Conclusions: 1. The presence of -589T/T genotype of the IL4-589C>T gene polymorphism and the -20A/A genotype of the DEFB1-20G>A gene polymorphism contributes to a high content of TNFα and IL-1β in the blood serum, and the carriage of -166His/His FCGR2A-166His>Arg gene polymorphism is associated with both higher level of TNFα, IL-1β, and a low concentration of IL-4, IL-10. 2. Complex carriers of FCGR2A166HisArg x DEFB152AA x DEFB120AA x IL4589TT genotypes in the patients with primary coxarthrosis increases the contents of TNFα, IL-1β cytokines by 1.5 and 1.7 times, respectively.

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Non-synonymous WNT16 polymorphisms alleles are associated with different osteoarthritis phenotypes

Cited by 7 publications

References 39 publications

Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Wnt16 signaling in bone homeostasis and osteoarthristis

Effect of IL4-589C>T, FCGR2A-166His>Arg, DEFB1-20G>A, DEFB1-52G>A gene polymorphisms on TNFα, IL-1β, IL-4, and IL-10 contents in the patients with primary hip osteoarthrosis

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