-
The Journal of Investigative Dermatology May 2023Psoriasis (PSO) and psoriatic arthritis (PSA) are inflammatory diseases with complex genetic and environmental contributions. Although studies have identified...
Psoriasis (PSO) and psoriatic arthritis (PSA) are inflammatory diseases with complex genetic and environmental contributions. Although studies have identified environmental and clinical associations with PSO/PSA, causality is difficult to establish. Mendelian randomization (MR) employs the random assortment of genetic alleles at birth to evaluate the causal impact of exposures. We systematically reviewed 27 MR studies in PSO/PSA examining health behaviors, comorbidities, and biomarkers. Exposures, including smoking, obesity, cardiovascular disease, and Crohn's disease, were causal for PSO and PSA, whereas PSO was causally associated with several comorbidities. These findings provide insights that can guide preventive counseling and precision medicine.
Topics: Infant, Newborn; Humans; Arthritis, Psoriatic; Mendelian Randomization Analysis; Psoriasis; Comorbidity; Biomarkers
PubMed: 36822971
DOI: 10.1016/j.jid.2022.11.014 -
The Journal of Antimicrobial... Aug 2020Improved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular...
Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.
BACKGROUND
Improved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular diagnostics.
METHODS
Adhering to PRISMA guidelines, in March 2018, we performed a systematic review of studies implicating mutations in resistance through sequencing and phenotyping before and/or after spontaneous resistance evolution, as well as allelic exchange experiments. We focused on the novel drugs bedaquiline, delamanid, pretomanid and the repurposed drugs clofazimine and linezolid. A database of 1373 diverse control MTB whole genomes, isolated from patients not exposed to these drugs, was used to further assess genotype-phenotype associations.
RESULTS
Of 2112 papers, 54 met the inclusion criteria. These studies characterized 277 mutations in the genes atpE, mmpR, pepQ, Rv1979c, fgd1, fbiABC and ddn and their association with resistance to one or more of the five drugs. The most frequent mutations for bedaquiline, clofazimine, linezolid, delamanid and pretomanid resistance were atpE A63P, mmpR frameshifts at nucleotides 192-198, rplC C154R, ddn W88* and ddn S11*, respectively. Frameshifts in the mmpR homopolymer region nucleotides 192-198 were identified in 52/1373 (4%) of the control isolates without prior exposure to bedaquiline or clofazimine. Of isolates resistant to one or more of the five drugs, 59/519 (11%) lacked a mutation explaining phenotypic resistance.
CONCLUSIONS
This systematic review supports the use of molecular methods for linezolid resistance detection. Resistance mechanisms involving non-essential genes show a diversity of mutations that will challenge molecular diagnosis of bedaquiline and nitroimidazole resistance. Combined phenotypic and genotypic surveillance is needed for these drugs in the short term.
Topics: Antitubercular Agents; Clofazimine; Diarylquinolines; Humans; Linezolid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Nitroimidazoles; Oxazoles; Pharmaceutical Preparations; Tuberculosis, Multidrug-Resistant
PubMed: 32361756
DOI: 10.1093/jac/dkaa136 -
Nutrients Sep 2021The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in... (Meta-Analysis)
Meta-Analysis
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein.
The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in adults with excessive body weight. The secondary aim was to investigate potential modifying effects of phenotyping. A systematic literature search in PubMed, Web of Science, and Cochrane Library identified 375 randomized controlled trials with 43 unique trials meeting the inclusion criteria. The Cochrane collaboration tool was used for a thorough risk of bias assessment. Based on 37 studies evaluating effects of dietary protein on body weight, the participants with increased protein intake (ranging from 18-59 energy percentage [E%]) were found to reduce body weight by 1.6 (1.2; 2.0) kg (mean [95% confidence interval]) compared to controls (isocaloric interventions with energy reduction introduced in certain studies). Individuals with prediabetes were found to benefit more from a diet high in protein compared to individuals with normoglycemia, as did individuals without the obesity risk allele (AA genotype) compared to individuals with the obesity risk alleles (AG and GG genotypes). Thus, diets rich in protein would seem to have a moderate beneficial effect on body weight management.
Topics: Adult; Body Mass Index; Body Weight; Diet, High-Protein; Dietary Proteins; Exercise; Female; Humans; Male; Middle Aged; Obesity; Overweight; Randomized Controlled Trials as Topic; Weight Gain; Weight Loss; Young Adult
PubMed: 34579069
DOI: 10.3390/nu13093193 -
Biomedicine & Pharmacotherapy =... Sep 2022Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary... (Review)
Review
Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.
Topics: Azetidines; Benzyl Compounds; Cytochrome P-450 CYP2C9; Genotype; Pharmacogenetics
PubMed: 36076616
DOI: 10.1016/j.biopha.2022.113536 -
Archives of Medical Science : AMS 2023Many studies are drawing attention to the associations of HOTAIR polymorphisms and susceptibility to breast cancer, while the results remain inconsistent. We conducted a... (Review)
Review
INTRODUCTION
Many studies are drawing attention to the associations of HOTAIR polymorphisms and susceptibility to breast cancer, while the results remain inconsistent. We conducted a meta-analysis on the association of four common HOTAIR polymorphisms with breast cancer susceptibility.
MATERIAL AND METHODS
Eligible published articles were searched in PubMed, Embase, Cochrane library databases and Web of Science databases up to July 2019. Odds ratios with 95% confidence intervals were used to identify potential links between lncRNA HOTAIR polymorphisms and the risk of breast cancer.
RESULTS
Our results showed no significance in all genetic models of all four SNPs. Pooled analyses detected crucial links between the rs1899663 polymorphism and decreased susceptibility to breast cancer in five genetic models rather than the dominant model in the hospital-based control subgroup. For the rs920778 polymorphism, we found that it significantly decreased breast cancer risk under recessive, homozygous and heterozygous models within the west Asian subgroup and increased breast cancer risk under allele and dominant models within the East Asian subgroup. Additionally, rs920778 polymorphism decreased breast cancer risk under recessive and heterozygous models in the hospital-based control subgroup. However, no significant association was observed between the rs4759314 polymorphism and breast cancer risk in overall and stratified analyses. For rs12826786 polymorphism, it was greatly associated with decreased breast cancer risk under recessive, homozygous and heterozygous models in the hospital-based control subgroup.
CONCLUSIONS
HOTAIR rs920778, rs1899663 and rs12826786 polymorphisms may contribute to breast cancer susceptibility.
PubMed: 36817654
DOI: 10.5114/aoms.2019.87537 -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
International Journal of Molecular... Apr 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and... (Meta-Analysis)
Meta-Analysis Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the "C" allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.
Topics: Humans; Amyotrophic Lateral Sclerosis; Aminopeptidases; Genome-Wide Association Study; Neurodegenerative Diseases; Prognosis; Biomarkers
PubMed: 37108335
DOI: 10.3390/ijms24087169 -
Dentistry Journal Nov 2022Genetic factors contribute to susceptibility and resistance to fluoride exposure. The aim of this systematic review was to identify alleles/genotypes of single... (Review)
Review
Genetic factors contribute to susceptibility and resistance to fluoride exposure. The aim of this systematic review was to identify alleles/genotypes of single nucleotide polymorphisms (SNPs) associated with dental fluorosis (DF) and to identify them as protective or risk factors. PubMed, ScienceDirect, Cochrane Library, Scopus and Web of Science were searched for articles; the last search was performed in August 2022. Human studies that analyzed the relationship between SNPs and DF published in English were included; systematic reviews and meta-analyses were excluded. Methodological quality was graded using the Joanna Briggs Institute checklist and risk of bias was assessed using the Cochrane Collaboration's tool. Eighteen articles were included, 44% of which showed high methodological quality and data from 5,625 participants aged 6 to 75 years were analyzed. The SNPs COL1A2, ESR2, DLX1, DLX2, AMBN, TUFT1, TFIP11, miRNA17, and SOD2 were considered risk factors, and ESR1, MMP20, and ENAM were considered protective factors. In conclusion, there are alleles and genotypes of different single nucleotide polymorphisms involved in increasing or decreasing the risk of developing dental fluorosis.
PubMed: 36354656
DOI: 10.3390/dj10110211 -
Cardiovascular Research Jul 2023Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This... (Meta-Analysis)
Meta-Analysis
Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98-35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34-1.50 and 1.27; 95% CI: 1.09-1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09-0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01-1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.
Topics: Female; Humans; Aortic Valve; Aortic Valve Stenosis; Hyperlipidemias; Lipoprotein(a); Risk Factors
PubMed: 37078819
DOI: 10.1093/cvr/cvad062 -
BioMed Research International 2022Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for... (Review)
Review
BACKGROUND
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer.
METHODS
A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were "Xeroderma pigmentosum", "XP", "XPC", "Nucleotide excision repair", "NER", "POLH", "Dry pigmented skin", and "UV sensitive syndrome" meshed with the terms "Skin cancer", "Melanoma", and "NMSC".
RESULTS
After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment.
CONCLUSIONS
Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life.
Topics: DNA Repair; Humans; Ichthyosis; Melanoma; Neurodegenerative Diseases; Quality of Life; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum
PubMed: 35898688
DOI: 10.1155/2022/8549532