Polymorphisms of the dopamine metabolic and signaling pathways are associated with susceptibility to motor levodopa-induced complications (MLIC) in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Dopamine replacement therapy remains the gold standard for symptomatic management of Parkinson's disease worldwide. However, most patients will develop debilitating motor levodopa-induced complications (MLIC) in the form of levodopa-induced dyskinesia (LID) and/or motor fluctuations (MF). This study aimed to conduct a systematic review and meta-analysis on the pharmacogenetic association between LID and MF with common genetic variants of the dopamine metabolic and signaling pathways. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Extracted studies include case-control studies evaluating the association between SLC6A3/DAT rs28363170 and rs393795; COMT rs4680 and rs4633; MAO-B rs1799836, BDNF rs6265, DRD1 rs4532, DRD2 rs1800497, DRD3 rs6280, and DRD5 rs6283 polymorphisms; and the overall risk of MLIC and its subtypes LID or MF. Genotypic frequency were tested for deviation from the Hardy-Weinberg equilibrium (HWE), and the genetic association was examined using the allelic (a vs. A), recessive (aa vs. Aa + AA), dominant (aa + Aa vs. AA), overdominant (Aa vs. aa + AA), homozygous (aa vs. AA), and heterozygous (Aa vs. AA and aa vs. aA) models. RESULTS: Fourteen studies were included in the meta-analysis. A significant association was found between COMT rs46809 polymorphisms with LID but not MF, with the association observable in Asians but not Caucasians. In Asians, the COMT rs4633 was significantly associated with the occurrence of both LID and MF. The MAO-B rs1799836 was associated with both MF and LID. Among all the dopamine receptor genes analyzed, only DRD2 exhibited an association with LID. No association was observed between the SLC6AT/DAT and BDNF genes with either LID or MF. CONCLUSION: Strong associations were observed between polymorphisms of genes regulating dopamine metabolism with the occurrence of LID and/or MF. The MAO-B rs1799836 may be potential for use as a general pharmacogenetic marker of MLIC, while the COMT rs4680 and rs4633 may be used as markers of LID in Asian ethnicities.

A Brief Analysis on Clinical Severity of Mandibulofacial Dysostosis Guion-Almeida Type.

OBJECTIVE: Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype-phenotype correlation in MFDM. METHODS: Forty articles comprising 156 patients were evaluated. The genotype-phenotype correlation was analyzed using a chi-square or Fisher's exact test. RESULTS: The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype-phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. CONCLUSION: Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype-phenotype relationships in this disease.

Serum IL-6/IL-10 ratio as a biomarker for the diagnosis and severity assessment of primary-open angle glaucoma.

OBJECTIVE: To assess the performance of serum cytokine IL-6 and IL-6/IL-10 ratio as biomarkers for the diagnosis of primary open-angle glaucoma (POAG) and for determining its progression. METHODS: In this study, 20 POAG patients and 21 healthy individuals from the Indonesian population were enrolled. The serum concentration of IL-6 and IL-10 were quantified. Comparative analysis was performed in addition to assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. RESULTS: POAG patients had a higher IL-6 (p < 0.0001) and IL-6/IL-10 ratio (p < 0.0001) than controls. Among the POAG subjects, advanced-stage patients exhibited a higher IL-6/IL-10 ratio than those in the early-moderate stage (p = 0.001; p = 0.006). The ROC curve analysis showed that both IL-6 level and IL-6/IL-10 ratio exhibited an excellent capability of diagnosing POAG (cut-off of 20.5 pg/mL (100% sensitivity and 94% specificity) and 4.4 (88% sensitivity and 94% specificity), respectively). Serum IL-6/IL-10 ratio displayed a better performance than IL-6 in discriminating POAG severity with cut-off of at least 6.6 (sensitivity of 86% and specificity of 90%) and 9.1 (sensitivity of 89% and specificity of 78%) classified according to C/D ratio and MD of VF, respectively. CONCLUSION: The balance between IL-6 and IL-10 serum levels is potentially useful in discriminating POAG severity.