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Genetic Association Between Growth Differentiation Factor 5 Single Nucleotide Polymorphism and Primary Knee Osteoarthritis in a Group of Egyptian Patients: A Pilot Study.

ABSTRACT: Aim:This study aimed to determine the genetic association between Growth Differentiation Factor 5 (GDF5) gene (rs143383 T/C) single nucleotide polymorphism (SNP) and primary knee osteoarthritis (OA) in a group of Egyptian patients. Patients and Methods:The study included 47 patients with primary knee OA and 40 apparently healthy control subjects. The disease was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Health Assessment Questionnaire (HAQ). Radiological assessment was done by Kellgren-Laurence (K/L) grading system. The genetic association of the SNP with primary knee OA was assessed by restriction fragment length polymorphism - polymerase chain reaction (RFLP-PCR). Results:The mean total WOMAC index was significantly higher in patients with TT genotype as compared to patients with CC and CT genotypes (P<0.001). Similarly, the HAQ score was significantly higher among patients with TT genotype when compared to patients with CT and CC genotypes (P<0.001). There was a statistically significant association between different GDF5 genotypes and K/L radiological grading of knee OA among the studied patients (P=0.029). No statistically significant association was detected on comparing the frequency distribution of GDF5 alleles and genotypes frequencies of the SNP in patients and healthy controls. Conclusion:There is a possible genetic association between GDF5 (rs143383) SNP and severity of primary knee OA, which might facilitate the detection of patients with high risk for disease progression. The present study did not detect an association between the SNP and development of primary knee OA.

SUBMITTER: Mohasseb DMF

PROVIDER: S-EPMC7045969 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Genetic Association Between Growth Differentiation Factor 5 Single Nucleotide Polymorphism and Primary Knee Osteoarthritis in a Group of Egyptian Patients: A Pilot Study.

Mohasseb Dia Mohamed Fahmy DMF Saba Emmanuel Kamal Aziz EKA Saad Neveen Lewis Mikhael NLM Sarofeem Amira Dimas Hanna ADH

Mediterranean journal of rheumatology 20190629 2

<h4>Aim</h4>This study aimed to determine the genetic association between Growth Differentiation Factor 5 (GDF5) gene (rs143383 T/C) single nucleotide polymorphism (SNP) and primary knee osteoarthritis (OA) in a group of Egyptian patients.<h4>Patients and methods</h4>The study included 47 patients with primary knee OA and 40 apparently healthy control subjects. The disease was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Health Assessment Questi ...[more]

PMID: 32185351

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Project description:AbstractPain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.

Project description:Acute myelogenous leukemia (AML) is a heterogeneous disease characterized by myeloid progenitor cells uncontrolled proliferation gradually replacing normal hematopoiesis. To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in AML, and chronic myeloid leukemia (CML) in relation to their disease prognostic criteria. The study included 136 subjects; 52 AML, 54 CML and 30 subjects as control group matched for age and sex. Routine investigations including CBC, bone marrow aspiration, flow cytometry biochemical investigations and cytogenetics and molecular study were performed accordingly. DNA extraction and SNP assay for TET2 gene polymorphism was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500. The mean age was 43.4?±?14.0 years in AML patients, 45.98?±?15.7 years in CML patients and 39.3?±?6.587 years in control group (p?>?0.05). The frequency of TET2 SNP rs 34402524 ranged from heterozygous to homozygous in both AML (46%, 54%) and CML (48%, 46.2%) groups but was mainly homozygous among the control (80%) group (p?=?0.012). TET2 SNP rs 2454206 was mainly wild in CML (65.4%) and control (63.3%) groups compared to AML as wild was only in (46%) and heterozygous in (44%) with only 10% being homozygous (p?=?0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all three group (AML CML and control) showing no statistical significance (p?=?0.528). Eventhough, higher non responders to treatment were among homozygous and heterozygous groups yet, response to therapy as respect to specific TET2 SNP showed no significant variation (p?>?0.05). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p?>?0.05) except for TET2 SNP rs 34402524 where homozygous cases had larger spleen size (p?=?0.019). TET2 SNP is common in Egyptian myeloid neoplasm. This is the first study in this field and further studies are recommended to investigate TET2 and relation to other hematological malignancies and leukemogenesis transformation.

Project description:BackgroundChronic myeloid leukemia (CML) is a myeloproliferative neoplasm where pathogenesis is based on the oncoprotein termed BCR-ABL1.1 TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies, including CML. The relation between TET2 acquisition and CML transformation and/or imatinib resistance is needed to be investigated.2.AimTo evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria.Materials & methodThe study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations, including CBC, bone marrow aspiration, biochemical investigations, and molecular study, were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism were done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.ResultsThe mean age was 45.98±15.7 yrs in CML patients and 39.3±6.587 yrs in the control group (p>0.05). TET2 SNP rs 34402524 was either heterozygous or homozygous in CML (48%, 46.2% respectively) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 wild type within CML was detected in 65.4% of patients and in controls was 63.3% (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p>0.05) yet, it was significantly related to spleen size in rs 34402524 where the homozygous group had larger spleen size and higher BCR-ABL1 levels six months after starting TKIs (p<0.05).Conclusions/recommendationTET2 SNP is common among Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with larger spleen size and higher BCR-ABL1 levels after six months of starting TKIs suggesting disease progression.

Project description:BackgroundKnee osteoarthritis is the most prevalent chronic musculoskeletal debilitating disease. Current treatments are only symptomatic, and to improve this, we need a robust prediction model to stratify patients at an early stage according to the risk of joint structure disease progression. Some genetic factors, including single nucleotide polymorphism (SNP) genes and mitochondrial (mt)DNA haplogroups/clusters, have been linked to this disease. For the first time, we aim to determine, by using machine learning, whether some SNP genes and mtDNA haplogroups/clusters alone or combined could predict early knee osteoarthritis structural progressors.MethodsParticipants (901) were first classified for the probability of being structural progressors. Genotyping included SNP genes TP63, FTO, GNL3, DUS4L, GDF5, SUPT3H, MCF2L, and TGFA; mtDNA haplogroups H, J, T, Uk, and others; and clusters HV, TJ, KU, and C-others. They were considered for prediction with major risk factors of osteoarthritis, namely, age and body mass index (BMI). Seven supervised machine learning methodologies were evaluated. The support vector machine was used to generate gender-based models. The best input combination was assessed using sensitivity and synergy analyses. Validation was performed using tenfold cross-validation and an external cohort (TASOAC).ResultsFrom 277 models, two were defined. Both used age and BMI in addition for the first one of the SNP genes TP63, DUS4L, GDF5, and FTO with an accuracy of 85.0%; the second profits from the association of mtDNA haplogroups and SNP genes FTO and SUPT3H with 82.5% accuracy. The highest impact was associated with the haplogroup H, the presence of CT alleles for rs8044769 at FTO, and the absence of AA for rs10948172 at SUPT3H. Validation accuracy with the cross-validation (about 95%) and the external cohort (90.5%, 85.7%, respectively) was excellent for both models.ConclusionsThis study introduces a novel source of decision support in precision medicine in which, for the first time, two models were developed consisting of (i) age, BMI, TP63, DUS4L, GDF5, and FTO and (ii) the optimum one as it has one less variable: age, BMI, mtDNA haplogroup, FTO, and SUPT3H. Such a framework is translational and would benefit patients at risk of structural progressive knee osteoarthritis.

Project description:INTRODUCTION:The role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several candidate genes have been identified to be associated with it. Among these genes are Bone Morphogenetic Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Transforming Growth Factor (TGF) signaling pathway. The knee is the commonly affected joint, and knee OA has an especially high prevalence in Asian population. AIM:To investigate associations between Single Nucleotide Polymorphisms (SNPs) rs12901499 in SMAD3 and rs921126 in the BMP5 gene with knee OA susceptibility in and around Lucknow, Uttar Pradesh, India. MATERIALS AND METHODS:SNPs rs12901499 in SMAD3 and rs921126 in BMP5 were genotyped in patients with knee OA and age- sex matched OA-free controls from our population. A total of 450 patients with knee OA and 458 controls were enrolled in the study. Venous blood samples were obtained from all cases as well as controls for PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Data was collected and entered in excel sheets. Statistical analyses of the data were performed using statistical software package SPSS version 16.0. Chi-square, Student's t-test and logistic regression tests were used to analyse the data. RESULTS:GA and GG genotypes of both SNPs (rs12901499 and rs921126), and variant G, were associated with a significantly increased risk of knee OA. A significantly increased risk of knee OA was associated with the genotype GG and GA of rs12901499 (p < 0.03 and p <0.004 respectively) and rs921126 (p< 0.0001 and p<0.001 respectively) compared with the AA genotype. In addition, those bearing at least one G allele (GG + GA) had a significantly increased risk of knee OA compared with those without the G allele (AA) in rs921126 (p< 0.0001). However, in rs12901499, significant association with the risk of knee OA was not found (p<0.4). On age and gender based stratification, the association between the risk of OA and rs921126 GG mutant compared with AA homozygotes was strong in both gender (adjusted OR= 2.93 for male and 2.25 for female) and in those aged >55 years (adjusted OR= 3.4), similarly in rs12901499, GG mutant compared with AA homozygote was strong in female (adjusted OR= 1.5) and in those aged >55 years (adjusted OR= 1.5). CONCLUSION:The results showed that both in SMAD3 rs12901499 and BMP5 921126, G allele is significantly associated with knee OA. A to G change and variant G genotype may contribute to knee OA risk in our study population of Lucknow.

Dataset Information

Genetic Association Between Growth Differentiation Factor 5 Single Nucleotide Polymorphism and Primary Knee Osteoarthritis in a Group of Egyptian Patients: A Pilot Study.

Publications

Genetic Association Between Growth Differentiation Factor 5 Single Nucleotide Polymorphism and Primary Knee Osteoarthritis in a Group of Egyptian Patients: A Pilot Study.

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