scholarly journals In Search of Biomarkers for Idiopathic Scoliosis: Leptin and BMP4 Functional Polymorphisms

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Svetla Nikolova ◽  
Vasil Yablanski ◽  
Evgeni Vlaev ◽  
Gergana Getova ◽  
Ventseslav Atanasov ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Early Stage ◽  
Population Sample ◽  
Rapid Progression ◽  
Promoter Polymorphisms ◽  
Functional Polymorphisms ◽  
Chi Squared ◽  
Bulgarian Population ◽  
Curve Severity ◽  
Control Study

Idiopathic scoliosis (IS) is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms of leptin (rs7799039) and BMP4 (rs4898820) with susceptibility to IS and curve severity was investigated in a Bulgarian population sample. The molecular detection of the genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. This case-control study revealed no statistically significant association between the functional polymorphisms of leptin and BMP4 and susceptibility to IS or curve progression (p>0.05). On the basis of these results the examined polymorphic variants of leptin and BMP4 could not be considered as genetic variants with predisposition effect or as risk factors for the progression of the curve. In addition, these results do not exclude a synergistic effect of the promoter polymorphisms of leptin and BMP4 in the etiology and pathogenesis of IS. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.

scholarly journals Role of the IL-6 Gene in the Etiopathogenesis of Idiopathic Scoliosis

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Svetla Nikolova ◽  
Milka Dikova ◽  
Dobrin Dikov ◽  
Assen Djerov ◽  
Gyulnas Dzhebir ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Case Control Study ◽  
Early Stage ◽  
Promoter Polymorphism ◽  
Case Control ◽  
Chi Squared ◽  
Bulgarian Population ◽  
Deformity Progression ◽  
Curve Severity ◽  
Control Study

Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6). The G/C polymorphism of the promoter region ofIL-6gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS) and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and theIL-6promoter polymorphism at -174 position (rs1800795 G/C) in Bulgarian population. Molecular detection of theIL-6genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. Our case-control study revealed a statistically significant association between theIL-6(-174 G/C) functional polymorphism and susceptibility to IS. In addition, a significant association between theIL-6(-174 G/C) polymorphism and curve severity was detected.IL-6gene could be considered as susceptibility and modifying factor of idiopathic scoliosis. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

scholarly journals Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Vasil Yablanski ◽  
Svetla Nikolova ◽  
Evgeni Vlaev ◽  
Alexey Savov ◽  
Ivo Kremensky
Keyword(s):  
Idiopathic Scoliosis ◽  
Early Stage ◽  
Population Sample ◽  
Promoter Polymorphism ◽  
European Population ◽  
Rapid Progression ◽  
Eastern European ◽  
Exact Test ◽  
Disease Modifier ◽  
Curve Severity

The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher’s Exact Test. The results indicated that the genotypes and alleles of TPH1 (rs10488682) are not correlated with curve severity, curve pattern, or bracing. Therefore, the examined polymorphic variant could not be considered as a genetic factor with modifying effect of IS. In conclusion, this case-control study revealed no statistically significant association between TPH1 (rs10488682) and progression of IS in Eastern European population sample. These preliminary results should be replicated in extended population studies including larger sample sizes. The identification of molecular markers for IS could be useful for a more accurate prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.

scholarly journals Association Study between Idiopathic Scoliosis and Polymorphic Variants of VDR, IGF-1, and AMPD1 Genes

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Svetla Nikolova ◽  
Vasil Yablanski ◽  
Evgeni Vlaev ◽  
Luben Stokov ◽  
Alexey Slavkov Savov ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Early Stage ◽  
Genetic Disorder ◽  
Three Dimensional ◽  
Restriction Enzymes ◽  
Case Control ◽  
Unknown Etiology ◽  
Rapid Progression ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies

Idiopathic scoliosis (IS) is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine with unknown etiology. For the aims of the current study we selected 3 single nucleotide polymorphisms with a low incidence of the polymorphic allele in Bulgarian population, AMPD1 (rs17602729), VDR (rs2228670), and IGF-1 (rs5742612), trying to investigate the association between these genetic polymorphisms and susceptibility to and progression of IS. The polymorphic regions of the genes were amplified by polymerase chain reaction (PCR). The PCR products were cleaved with the appropriate restriction enzymes. The statistical analysis was performed by Pearson’s chi-squared test. A value of p<0.05 was considered to be statistically significant. In conclusion, this case-control study revealed no statistically significant association between the VDR, IGF-1, and AMPD1 polymorphisms and the susceptibility to IS or curve severity in Bulgarian patients. Replication case-control studies will be needed to examine the association between these candidate-genes and IS in different populations. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.

scholarly journals The Association Study of Calmodulin 1 Gene Polymorphisms with Susceptibility to Adolescent Idiopathic Scoliosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Zhang ◽  
Zuchao Gu ◽  
Guixing Qiu
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Case Control Study ◽  
Case Control ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Curve Severity ◽  
The Relationship ◽  
Control Study ◽  
Main Curve

Objective.Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between calmodulin 1 (CALM1) gene and AIS predisposition, to identify the relationship between the genotypes of the SNPs and the clinical phenotypes of AIS.Methods.146 AIS patients and 146 healthy controls were enrolled into this case-control study. 12 single nucleotide polymorphisms (SNPs) candidates in CALM1 gene were selected to determine the relationship between CALM1 gene and AIS predisposition. Case-only study was performed to determine the effects of these variants on the severity of the condition.Results.Three SNPs from 12 candidates were found to be associated with AIS predisposition. The ORs were observed as 0.549 (95% CI 0.3519–0.8579,P=0.0079), 0.549 (95% CI 0.3519–0.8579,P=0.0079), and 1.6139 (95% CI 1.0576–2.4634,P=0.0257) for rs2300496, rs2300500, and rs3231718, respectively. There was no statistical difference between main curve, severity, and genotype distributions of all of 12 SNPs.Conclusion.Genetic variants of CALM1 gene are associated with AIS susceptibility.

scholarly journals Association between Estrogen Receptor Alpha Gene Polymorphisms and Susceptibility to Idiopathic Scoliosis in Bulgarian Patients: A Case-Control Study

2015 ◽  
Vol 3 (2) ◽  
pp. 278-282 ◽  
Author(s):  
Svetla Nikolova ◽  
Vasil Yablanski ◽  
Evgeni Vlaev ◽  
Luben Stokov ◽  
Alexey Savov ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Idiopathic Scoliosis ◽  
Estrogen Receptor Alpha ◽  
Case Control Study ◽  
Early Stage ◽  
Case Control ◽  
Receptor Alpha ◽  
Estrogen Receptor Alpha Gene ◽  
Alpha Gene ◽  
Control Study

BACKGROUND: The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors.AIM: Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis.MATERIAL AND METHODS: We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis. Molecular detection of the restriction polymorphisms XbaI and PvuII was performed by polymerase chain reaction following by restriction fragment length polymorphism. The statistical analysis was performed by Pearson's chi-squared test.RESULTS: Our case-control study showed statistically significant association between the PvuII polymorphism and susceptibility to idiopathic scoliosis and curve progression. No genotype or allele of XbaI polymorphism was found to be correlated with the onset or severity of the disease.CONCLUSIONS: The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

scholarly journals Serum Biomarker Signature-Based Liquid Biopsy for Diagnosis of Early-Stage Pancreatic Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2887-2894 ◽  
Author(s):  
Linda D. Mellby ◽  
Andreas P. Nyberg ◽  
Julia S. Johansen ◽  
Christer Wingren ◽  
Børge G. Nordestgaard ◽  
...  
Keyword(s):  
Case Control Study ◽  
Early Stage ◽  
Stage Iv ◽  
The United States ◽  
Case Control ◽  
Stage I ◽  
Serum Biomarker ◽  
Patient Cohort ◽  
Biomarker Signature ◽  
Control Study

Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of < 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort. Patients and Methods The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC. Results Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96. Conclusion This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.

Correlation Between Hump Dimensions and Curve Severity in Idiopathic Scoliosis Before and After Conservative Treatment

Spine ◽  
2018 ◽  
Vol 43 (2) ◽  
pp. 114-119 ◽  
Author(s):  
Angelo Gabriele Aulisa ◽  
Vincenzo Guzzanti ◽  
Carlo Perisano ◽  
Emanuele Marzetti ◽  
Amerigo Menghi ◽  
...  
Keyword(s):  
Conservative Treatment ◽  
Idiopathic Scoliosis ◽  
Before And After ◽  
Curve Severity

scholarly journals Persistence of Viremia and Production of Neutralizing Antibodies Differentially Regulated by Polymorphic APOBEC3 and BAFF-R Loci in Friend Virus-Infected Mice

2010 ◽  
Vol 84 (12) ◽  
pp. 6082-6095 ◽  
Author(s):  
Sachiyo Tsuji-Kawahara ◽  
Tomomi Chikaishi ◽  
Eri Takeda ◽  
Maiko Kato ◽  
Saori Kinoshita ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Early Stage ◽  
Chromosome 15 ◽  
Cell Repertoire ◽  
Viral Loads ◽  
Functional Polymorphisms ◽  
B Cell Repertoire ◽  
Retroviral Replication ◽  
Different Strains ◽  
Host Genes

ABSTRACT Several host genes control retroviral replication and pathogenesis through the regulation of immune responses to viral antigens. The Rfv3 gene influences the persistence of viremia and production of virus-neutralizing antibodies in mice infected with Friend mouse retrovirus complex (FV). This locus has been mapped within a narrow segment of mouse chromosome 15 harboring the APOBEC3 and BAFF-R loci, both of which show functional polymorphisms among different strains of mice. The exon 5-lacking product of the APOBEC3 allele expressed in FV-resistant C57BL/6 (B6) mice directly restricts viral replication, and mice lacking the B6-derived APOBEC3 exhibit exaggerated pathology and reduced production of neutralizing antibodies. However, the mechanisms by which the polymorphisms at the APOBEC3 locus affect the production of neutralizing antibodies remain unclear. Here we show that the APOBEC3 genotypes do not directly affect the B-cell repertoire, and mice lacking B6-derived APOBEC3 still produce FV-neutralizing antibodies in the presence of primed T helper cells. Instead, higher viral loads at a very early stage of FV infection caused by either a lack of the B6-derived APOBEC3 or a lack of the wild-type BAFF-R resulted in slower production of neutralizing antibodies. Indeed, B cells were hyperactivated soon after infection in the APOBEC3- or BAFF-R-deficient mice. In contrast to mice deficient in the B6-derived APOBEC3, which cleared viremia by 4 weeks after FV infection, mice lacking the functional BAFF-R allele exhibited sustained viremia, indicating that the polymorphisms at the BAFF-R locus may better explain the Rfv3-defining phenotype of persistent viremia.

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