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Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis.

ABSTRACT: 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.

SUBMITTER: Yablanski V

PROVIDER: S-EPMC4884859 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis.

Yablanski Vasil V Nikolova Svetla S Vlaev Evgeni E Savov Alexey A Kremensky Ivo I

Journal of biomarkers 20160516

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 s ...[more]

PMID: 27293961

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Project description:Current prediction models of mortality in idiopathic pulmonary fibrosis (IPF), which are based on clinical and physiological parameters, have modest value in predicting which patients will progress. In addition to the potential for improving prognostic models, identifying genetic and molecular features that are associated with IPF mortality may provide insight into the underlying mechanisms of disease and inform clinical trials.To determine whether the MUC5B promoter polymorphism (rs35705950), previously reported to be associated with the development of pulmonary fibrosis, is associated with survival in IPF.Retrospective study of survival in 2 independent cohorts of patients with IPF: the INSPIRE cohort, consisting of patients enrolled in the interferon-?1b trial (n = 438; December 15, 2003-May 2, 2009; 81 centers in 7 European countries, the United States, and Canada), and the Chicago cohort, consisting of IPF participants recruited from the Interstitial Lung Disease Clinic at the University of Chicago (n = 148; 2007-2010). The INSPIRE cohort was used to model the association of the MUC5B genotype with survival, accounting for the effect of matrix metalloproteinase 7 (MMP-7) blood concentration and other demographic and clinical covariates. The Chicago cohort was used for replication of findings.The primary end point was all-cause mortality.The numbers of patients in the GG, GT, and TT genotype groups were 148 (34%), 259 (59%), and 31 (7%), respectively, in the INSPIRE cohort and 41 (28%), 98 (66%), and 9 (6%), respectively, in the Chicago cohort. The median follow-up period was 1.6 years for INSPIRE and 2.1 years for Chicago. During follow-up, there were 73 deaths (36 GG, 35 GT, and 2 TT) among INSPIRE patients and 64 deaths (26 GG, 36 GT, and 2 TT) among Chicago patients. The unadjusted 2-year cumulative incidence of death was lower among patients carrying 1 or more copies of the IPF risk allele (T) in both the INSPIRE cohort (0.25 [95% CI, 0.17-0.32] for GG, 0.17 [95% CI, 0.11-0.23] for GT, and 0.03 [95% CI, 0.00-0.09] for TT) and the Chicago cohort (0.50 [95% CI, 0.31-0.63] for GG, 0.22 [95% CI, 0.13-0.31] for GT, and 0.11 [95% CI, 0.00-0.28] for TT). In the INSPIRE cohort, the TT and GT genotypes (risk for IPF) were associated with improved survival compared with GG (hazard ratios, 0.23 [95% CI, 0.10-0.52] and 0.48 [95% CI, 0.31-0.72], respectively; P < .001). This finding was replicated in the Chicago cohort (hazard ratios, 0.15 [95% CI, 0.05-0.49] and 0.39 [95% CI, 0.21-0.70], respectively; P < .002). The observed association of MUC5B with survival was independent of age, sex, forced vital capacity, diffusing capacity of carbon monoxide, MMP-7, and treatment status. The addition of the MUC5B genotype to the survival models significantly improved the predictive accuracy of the model in both the INSPIRE cohort (C = 0.71 [95% CI, 0.64-0.75] vs C = 0.68 [95% CI, 0.61-0.73]; P < .001) and the Chicago cohort (C = 0.73 [95% CI, 0.62-0.78] vs C = 0.69 [95% CI, 0.59-0.75]; P = .01).Among patients with IPF, a common risk polymorphism in MUC5B was significantly associated with improved survival. Further research is necessary to refine the risk estimates and to determine the clinical implications of these findings.

Project description:BackgroundChildren with adolescent idiopathic scoliosis (AIS) have reduced quality of life related to poor self-image, perhaps because of cosmetic concerns. However, there has not been a large-database epidemiologic study on the association between psychiatric disorders and scoliosis.Questions/purposesUsing the Korean National Health Insurance database, we asked: (1) How common are psychiatric disorders among children with AIS? (2) After controlling for gender, age, insurance type, and residential district, are psychiatric disorders more common among children with AIS than among age-matched controls?MethodsA retrospective analysis was conducted using sample datasets from the Health Insurance Review and Assessment Service from 2012 to 2016, which is a 10% randomly extracted sample of total inpatients and outpatients each year. The mean number of total patients in each dataset was 1,047,603 ± 34,534. The mean number of children with AIS was 7409 ± 158 for each year. The age criteria was 10 to 19 years for the matching. Mood disorders, anxiety disorders, and behavioral disorders were selected as disorders possibly associated with AIS. We identified children with AIS who had any of the disorders above, and we obtained the prevalence of these disorders based on diagnostic codes. As an exploratory analysis, clinically meaningful variables were selected among the available codes in the dataset, and a univariable logistic regression test was performed for each variable. A multivariable logistic regression test with advanced variables was performed to identify the adjusted odds ratios of psychiatric disorders in children with AIS.ResultsThe median (range) prevalence of psychiatric disorders in children with AIS from 2012 to 2016 was 7% (6% to 7%). Compared with children who did not have AIS, and after controlling for gender, age, insurance type, and residential district, children with AIS were more likely to have psychiatric disorders in all 5 years. The adjusted ORs of psychiatric disorders in children with AIS compared with children who did not have AIS ranged from 1.47 to 1.74 (2012: OR 1.60 [95% CI 1.46 to 1.75]; p < 0.001; 2013: OR 1.73 [95% CI 1.58 to 1.89]; p < 0.001; 2014: OR 1.74 [95% CI 1.59 to 1.91]; p < 0.001; 2015: OR 1.71 [95% CI 1.56 to 1.88]; p < 0.001; 2016: OR 1.47 [95% CI 1.33 to 1.62]; p < 0.001).ConclusionConsidering the higher prevalence of psychiatric disorders in children with AIS compared with children who did not have AIS, children with AIS and their parents should be counseled about the increased risk of deteriorating mental health of the patients, and surgeons should provide early referral to pediatric psychiatrists. Further studies should investigate the effect of the factors related to AIS, such as curve type, Cobb angle, and treatment modality.Level of evidenceLevel III, prognostic study.

Project description:ObjectiveTo analyze the correlation between the polymorphism on interleukin 6 (IL-6) gene promoter region-174 locus and adolescent idiopathic scoliosis (AIS), including the susceptibility, the bracing effectiveness, and the possible mechanism.MethodsThe 182 AIS patients and 210 healthy controls who met the inclusion criteria between January 2013 and January 2016 were collected as research objects. The genotype of IL-6 gene promoter region-174 locus, the serum IL-6, the bone mineral density (BMD) of femoral neck and vertebrae (L 1-4), and the bone metabolism parameters, including bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate resistant acid phosphatase 5b (TRACP-5b), urine Ca, and urine Ca/Cr, were detected. All research objects were divided into the AIS group and the control group according to whether they had AIS, the GG, CG, CC groups according to their genotype, and progression-free group and progression group according to the therapeutic effectiveness of 1-year bracing treatment. Statistical analysis for the indexes were conducted respectively.ResultsThere were significant differences in AIS history, BMD of femoral neck and lumbar vertebrae between the AIS group and control group ( P<0.05). According to the therapeutic effecitveness of 1-year bracing treatment, 182 AIS patients were divided into progression-free group in 110 cases and progression group in 72 cases. The results of single factor analysis showed that there were significant differences in the genotype and allele distribution of IL-6 gene promoter region-174 locus, BMD of femoral neck and lumbar vertebrae, IL-6, TRACP-5b, urine Ca, and urine Ca/Cr between the progression-free group and progression group ( P<0.05). The results of multivariable analysis showed that the BMD of lumbar vertebrae, TRACP-5b, and urine Ca were the influencing factors of bracing efficacy ( P<0.05). According to the results of genotype detection, all research objects were divided into GG group in 264 cases, CG group in 104 cases, and CC group in 24 cases. The IL-6, TRACP-5b, urine Ca, and urine Ca/Cr of GG type carriers were higher and BMD of femoral neck and lumbar vertebrae were lower when compared with the CG and CC type carriers ( P<0.05). The BMD of lumbar vertebrae of CG type carriers was lower than that of CC type carriers ( P<0.05).ConclusionThe polymorphism of IL-6 genepromoter region-174 locus wasn't correlated with the AIS susceptibility, but it was correlated (not independently correlated) with the scoliosis progression under bracing treatment, and the risk for G-carried patients was higher. The mechanism may be that the polymorphism affected the IL-6 expression level and eventually affected the BMD of AIS patients through the bone metabolism.

Dataset Information

Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis.

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Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis.

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