Significant association of DRD2 enhancer variant rs12364283 with heroin addiction in a Pakistani population.

The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed.

Testing genetic modifiers of behavior and response to atomoxetine in autism spectrum disorder with ADHD.

Background: Frequent non-pathogenic genetic variants may act as moderators of phenotypic severity for complex disorders such as autism spectrum disorder (ASD). We previously identified polymorphisms affecting mRNA expression of candidate genes, including tryptophan hydroxylase 2 (), dopamine beta hydroxylase (), and dopamine transporter ().

Method: We compare genotypes and (1) clinical response to atomoxetine, (2) scores from the Autism Diagnostic Interview-Revised (ADI-R), and (3) severity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms in a cohort of patients with ASD from multiple study sites.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits.

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3'UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects.

Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs) in lymphoblast cell lines (LCL) and in polysomal fractions.

Working memory in pregnant women: Relation to estrogen and antepartum depression.

This article is part of a Special Issue "Estradiol and cognition". Subjective changes in concentration and memory are commonly reported by women during the second or third trimesters of pregnancy, but the nature of the problem is poorly understood. We hypothesized that these self-reports might reflect difficulties in working memory (WM).

Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity.

Rationale: Dopamine β-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine in the central nervous system and peripherally. DBH variants are associated with large changes in circulating DBH and implicated in multiple disorders; yet causal relationships and tissue-specific effects remain unresolved.

Objective: To characterize regulatory variants in DBH, effect on mRNA expression, and role in modulating sympathetic tone and disease risk.

Serotonin 2A receptor gene (HTR2A) regulatory variants: possible association with severity of depression symptoms in children with autism spectrum disorder.

Objective And Background: Our aim was to characterize the association of 2 functional single nucleotide polymorphisms (rs6311 and rs6314) in the serotonin 2A receptor gene (HTR2A) with severity of depression symptoms in children with autism spectrum disorder. These polymorphisms have been shown to be associated with depression symptom severity and response to selective serotonin reuptake inhibitor drugs in adults with diagnosed depressive disorder.

Methods: Parents of 104 children with autism spectrum disorder rated their children's depressive symptoms using a validated scale based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition.

Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale.

Association study of the estrogen receptor gene ESR1 with postpartum depression--a pilot study.

Perinatal mood disorders, such as postpartum depression (PPD), are costly for society, with potentially serious consequences for mother and child. While multiple genes appear to play a role in PPD susceptibility, the contributions of specific genetic variations remain unclear. Previously implicated as a candidate gene, the estrogen receptor alpha gene (ESR1) is a key player in mediating hormonal differences during pregnancy and the postpartum period.

Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk.

Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels.

Dopamine transporter gene variant affecting expression in human brain is associated with bipolar disorder.

The gene encoding the dopamine transporter (DAT) has been implicated in CNS disorders, but the responsible polymorphisms remain uncertain. To search for regulatory polymorphisms, we measured allelic DAT mRNA expression in substantia nigra of human autopsy brain tissues, using two marker SNPs (rs6347 in exon 9 and rs27072 in the 3'-UTR). Allelic mRNA expression imbalance (AEI), an indicator of cis-acting regulatory polymorphisms, was observed in all tissues heterozygous for either of the two marker SNPs.

Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

Background: Genetic variation in mRNA expression plays a critical role in human phenotypic diversity, but it has proven difficult to detect regulatory polymorphisms - mostly single nucleotide polymorphisms (rSNPs). Additionally, variants in the transcribed region, termed here 'structural RNA SNPs' (srSNPs), can affect mRNA processing and turnover. Both rSNPs and srSNPs cause allelic mRNA expression imbalance (AEI) in heterozygous individuals.

Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain: dissection of epigenetic and genetic factors.

A pVNTR repeat polymorphism located in the promoter region of the X-linked MAOA gene has been associated with mental disorders. To explore the effect of polymorphisms and epigenetic factors on mRNA expression, we have measured allelic expression imbalance (AEI) in female human brain tissue, employing two frequent marker single nucleotide polymorphisms (SNPs) in exon 8 (T890G) and exon 14 (C1409T) of MAOA. This approach compares one allele against the other in the same subject.

Functional characterization of the peptide transporter PEPT2 in primary cultures of human upper airway epithelium.

This study characterizes the expression and function of the peptide transporter hPepT2 (SLC15A2) in differentiated primary cultures of human upper airway lung epithelia obtained from six human donors. Genotype analysis of a SNP in exon 15 of hPepT2 genotypes in six donors revealed an expected distribution of the two main variants present at similar frequency (two AA homozygotes, two BB homozygotes, and two AB heterozygotes). Real-time PCR analysis of the hPepT2 mRNA message revealed no significant differences among genotypes.

Single nucleotide polymorphism genotyping using allele-specific PCR and fluorescence melting curves.

We present a PCR method for identification of single nucleotide polymorphisms (SNPs), using allele-specific primers designed for selective amplification of each allele. Matching the SNP at the 3' end of the forward or reverse primer, and additionally incorporating a 3' mismatch to prevent amplification of the incorrect allele, results in selectivity of the allele-specific primers. DNA melting analysis with fluorescent SYBR Green affords detection of the PCR products.