Association of α2A-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals modifies the antiplatelet response to sympathetic stimulation. The aim of this study was to investigate the effect of ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms (SNPs) of ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP) inhibition was detected by thromboelastography (TEG®).</p><p><b>RESULTS</b>The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033), rs3750625 (P = 0.020) and CYP2C19*2 (P = 0.002) were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males, but not in females.</p><p><b>CONCLUSION</b>ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.</p>

Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases

OBJECTIVE: ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. METHODS: Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. RESULTS: Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. CONCLUSION: Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.

The rs10885122 polymorphism of the adrenoceptor alpha 2A (ADRA2A) gene in Euro-Brazilians with type 2 diabetes mellitus

Objective To investigate the association of the rs10885122G>T polymorphism in the ADRA2A gene in a Euro-Brazilian sample of healthy (controls) and type 2 diabetic (T2D) subjects. Subjects and methods We used fluorescent probes (TaqMan) to genotype 241 subjects, that is, 121 healthy and 120 T2D subjects, who were classified based on the Brazilian Diabetes Association (2013) and American Diabetes Association (2014) criteria. Results The genotype and allele frequencies showed no significant (P > 0.05) difference between the two studied groups. The minor allele (T) frequencies (95%CI) for rs10885122 were 19% (14-24%) and 20% (15-26%) for healthy and T2D groups, respectively. Carriers of the T allele (genotypes GT+TT) were significantly associated (P = 0.016) with approximately a 7-kg body weight reduction compared with the genotype GG, which was only found in the T2D group. Conclusion The rs10885122G>T polymorphism of the ADRA2A gene was not associated with T2D in Euro-Brazilians, and carriers of the T allele had lower body weight in the presence of T2D. Arch Endocrinol Metab. 2015;59(1):29-33 .

Regional Brain Perfusion before and after Treatment with Methylphenidate According to the MspI Polymorphism of the Alpha-2A Adrenergic Receptor Gene in Children with Attention-Deficit Hyperactivity Disorder

OBJECTIVES: Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfusion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD. METHODS: Thirty seven drug-naive ADHD children (8.9+1.8 years old, M=32, F=5) were genotyped. Baseline single-photon emission computed tomography (SPECT) and clinical assessments were performed for ADHD children. After treatment with methylphenidate for eight weeks, SPECT and clinical assessment were repeated. RESULTS: No differences in baseline clinical assessments or cerebral perfusion were observed according to the MspI genotype. However, after treatment, ADHD children with the G/G genotype at the MspI polymorphism showed hyperperfusion in the right cerebellar declive (p=.001, uncorrected) and hypoperfusion in the left lentiform nucleus and left cingulate gyrus (p<.001 and p=.001, uncorrected), compared to children without the G/G genotype. CONCLUSION: Although the results of this study should be interpreted cautiously, they suggest a possible role of the MspI polymorphisms of the ADRA2A gene in methylphenidate-induced changes in cerebral perfusion.

No Evidence of Association of the Alpha-2A-Adrenergic Receptor Gene with Methylphenidate Response in Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: The aim of this study was to examine the association of the ADRA2A MspI and DraI polymorphisms with methylphenidate (MPH) response in Korean children with ADHD. METHODS: The present study included 112 children and adolescents with ADHD (mean age=9.1+/-2.1 years), consisting of 92 boys (82.1%) and 20 girls (17.9%). ADHD was diagnosed based on the DSM-IV criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). For the clinical evaluation of the ADHD subjects, the ADHD Rating Scale-IV (ADHD-RS) and Clinical Global Impression (CGI) were administered at baseline and 8 weeks after MPH treatment. ADRA2A MspI and DraI polymorphisms were genotyped. The chi2 test was used to evaluate the relationship between the ADRA2A genotype and the response to MPH. The correlation between the genotype of ADRA2A and the change in the ADHD-RS scores after MPH treatment was assessed using the analysis of variance test and t-test. The significance level was set at p=0.01. RESULTS: No significant association was found between the genotypes of the ADRA2A MspI or DraI polymorphisms and MPH treatment response according to the CGI-improvement score (p>0.05). Comparing the changes in ARS scores after MPH treatment according to the genotypes of the MspI or DraI polymorphisms, we found no significant differences between subjects with different genotypes (p>0.05). CONCLUSION: Our results do not support the significant association between the MspI genotype and MPH response in Korean ADHD subjects, which was previously reported. In addition, we document no evidence of association between the DraI polymorphism and MPH treatment response in the Korean ADHD population.