Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe

Evoked Potentials in Patients With Wilson Disease

INTRODUCTION Wilson disease (WD) is an inherited disorder of copper metabolism presenting with a variety of symptoms but commonly as a liver or neuropsychiatric disease. Abnormal evoked responses are constantly found among patients with neurologic manifestations and sometimes in patients with hepatic presentation or in presymptomatic siblings. The aim of our study was to assess visual and brainstem auditory evoked potentials (BAEP) in patients with various presentation of WD. METHODS Visual evoked potentials (VEP) were performed in 36 WD patients and BAEP were done in 37 WD patients. RESULTS Brainstem auditory evoked potentials were normal in patients with isolated hepatic presentation, whereas they were abnormal in 93.5% of patients with neurologic symptoms. There was significant prolongation of the latencies of the III and V waves and of the interpeak III-V and I-V latencies in comparison with the healthy controls (T-test P = 0). Abnormal VEP were observed in 81% of the patients including six of seven neurologically asymptomatic patients. The values of N75, P100, and N145 latencies were significantly longer in all patients than in healthy controls (T-test). CONCLUSIONS The data showed that VEP and BAEP are more frequently abnormal in WD than previously reported. The abnormal VEP and BAEP even without clinical signs and brain MRI abnormalities point to subclinical involvement of visual and auditory pathways caused by copper toxicity. Because VEP and BAEP are noninvasive and widely available, they should be performed in all patents with WD

No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample

The µ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the µ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results. The aim of the current study was to examine whether this polymorphism was associated with heroin dependence in a large Bulgarian cohort of 1842 active users and 1451 population controls. SNP genotyping was done using Real-Time PCR TaqMan technology. Association analyses were conducted, separately for Roma and non-Roma participants. Our results suggest that there is no direct effect of 118A>G genotype on the risk for heroin dependence among active heroin users

Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V

Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal peripheral neuropathies inherited in an autosomal dominant fashion. Our previous genetic and physical mapping efforts localized the responsible gene(s) to a well-defined region on human chromosome 7p. Here, we report the identification of four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with CMT2D and dSMA-V. This is the first example of an aminoacyl tRNA synthetase being implicated in a human genetic disease, which makes genes that encode these enzymes relevant candidates for other inherited neuropathies and motor neuron diseases

The First Genomewide Interaction and Locus-Heterogeneity Linkage Scan in Bipolar Affective Disorder: Strong Evidence of Epistatic Effects between Loci on Chromosomes 2q and 6q

We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies