47,354 research outputs found
Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAa receptor B3 subunit genes
Molecular genetic research has identified promising markers of alcohol dependence, including alleles of the D2 dopamine receptor (DRD2) and the GABAA receptor ¬3 subunit (GABRB3) genes. Whether such genetic risk manifests itself in stronger alcohol-related outcome expectancies, or in difficulty resisting alcohol, is unknown. In the present study, A1+ (A1A1 and A1A2 genotypes) and A1- (A2A2 genotype) alleles of the DRD2 and G1+ (G1G1 and G1 non-G1 genotypes) and G1- (non-G1 non-G1 genotype) alleles of the GABRB3 were determined in a group of 56 medically-ill patients diagnosed with alcohol dependence. Mood-related Alcohol Expectancy (AE) and Drinking Refusal Self-Efficacy (DRSE) were assessed using the Drinking Expectancy Profile (Young and Oei, 1996). Patients with the DRD2 A1+ allele, compared to those with the DRD2 A1- allele, reported lower DRSE in situations of social pressure (p=. 009). Similarly, lower DRSE was reported under social pressure by patients with the GABRB3 G1+ allele when compared to those with the GABRB3 G1- allele (p=.027). Patients with the GABRB3 G1+ allele also revealed reduced DRSE in situations characterized by negative affect than patients with the GABRB3 G1- alleles (p=. 037). Patients carrying the GABRB3 G1+ allele showed stronger AE relating to negative affective change (for example, increased depression) than their GABRB3 G1- counterparts (p=. 006). Biological influence in the development of some classes of cognitions is hypothesized. The clinical implications, particularly with regard to patient-treatment matching and the development of an integrated psychological and pharmacogenetic approach are discussed
Association of polymorphisms in pulmonary surfactant protein A1 and A2 genes with high-altitude pulmonary edema
Study objectives: A potential pathogenetic cofactor for the development of high-altitude pulmonary edema (HAPE) is an increase in capillary permeability, which could occur as a result of an inflammatory reaction and/or free-radical-mediated injury to the lung. Pulmonary surfactant protein A (SP-A), the most abundant surfactant protein, has potent antioxidant properties and protects unsaturated phospholipids and growing cells from oxidative injury. Single-nucleotide polymorphisms (SNPs) in SP-A1 and SP-A2, genes encoding SP-A, have been associated with susceptibility to respiratory distress syndrome, COPD, and pulmonary infections. In view of the protective role of SP-A against inflammatory reactions and oxidative damage, the two underlying mechanisms in development of HAPE, we examined the association of constitutional susceptibility to HAPE with polymorphisms in SP-A1 and SP-A2. Design: A cross-sectional case-control study. Setting: Blood samples were collected at an altitude (≥ 3,500 m). Participants: Twelve low-altitude native (LAN) subjects with a history of HAPE, 15 healthy LAN sojourners without a history of HAPE (LAN control subjects), and 19 healthy high-altitude natives (HANs) without a history of HAPE (HAN control subjects). Measurements: The SNPs in four exons and intermediate introns of the SP-A1 and SP-A2 were screened by polymerase chain reaction and sequencing. Biochemical parameters related to oxidative stress (malondialdehyde and reduced glutathione in RBC) and membrane permeability (circulating levels of lactate dehydrogenase) were measured in plasma. Results: Allele frequencies of three loci in SP-A1 and one in SP-A2 were significantly different between LAN HAPE patients (SP-A1 C1101T: C allele, 36.4% and T allele, 63.6%; SP-A1 T3192C: T allele, 61.1% and C allele, 38.9%; SP-A1 T3234C: T allele, 61.1% and C allele, 38.9%; and SP-A2 A3265C: A allele, 21.4% and C allele, 78.6%) and LAN control subjects (SP-A1 C1101T: C allele, 8.3% and T allele, 91.7%; SP-A1 T3192C: T allele, 15% and C allele, 85%; SP-A1 T3234C: T allele, 15% and C allele, 85%; and SP-A2 A3265C: A allele, 37.5% and C allele, 62.5%) [C1101T odds ratio [OR], 6.3 with 95% confidence interval (CI), 2.8 to 14.3; T3192C OR, 8.9 with 95% CI, 4.5 to 17.6; T3234C OR, 8.9 with 95% CI, 4.5 to 17.6; and A3265C OR, 2.2 with 95% CI, 1.2 to 4.1 (p ≤ 0.01)]. Heterozygous individuals, with respect to SP-A1 C1101T and SP-A2 A3265C, showed less severity in oxidative damage in comparison with homozygous subjects (SP-A1 T1101 and SP-A2 C3265). Conclusion: The polymorphisms in SP-A1 (C1101T, T3192C, and T3234C) and SP-A2 (A3265C) might be one of the genetic factors contributing to susceptibility to HAPE
A note on the evaluation of a beta-casein variant in bovine breeds by allele-specific PCR and relevance to β-casomorphin
peer-reviewedThis work was supported by Enterprise Ireland and by a Teagasc Walsh fellowship to A.F. Keating.Two genetic variants of the bovine β-casein gene (A1 and B) encode a histidine residue at codon 67, resulting in potential liberation of a bioactive peptide, β-casomorphin, upon digestion. An allele-specific PCR (AS-PCR) was evaluated to distinguish between the β-casomorphin-releasing variants (A1 and B) and the non-releasing variants. AS-PCR successfully distinguished β-casein variants in 41 of 42 animals as confirmed by sequence analysis. Overall, while the incidence of the homozygous A1 and B animals (i.e., homozygous for the histidine residue; 21.4%) was lower than that for animals without the histidine residue (30.9% respectively), 69% of animals carried at least one allele for the histidine residue at codon 67.Teagasc Walsh Fellowship ProgrammeEnterprise Irelan
A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?
Addiction to a wide range of substances of abuse has been suggested to reflect a ‘Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D(2) receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30–40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity
Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their interaction with obesity
Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on almost all the executive variables, but no significant 'DRD4 7R-allele status' effects were observed for any of the executive variables analyzed. There was a significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions
The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: Associations and evidence for gene-environment correlation and gene-environment interaction
ObjectiveS: Research implicates the A1 allele of the dopamine D2 receptor gene (DRD2) Taq1A polymorphism in the development of depression and anxiety. Furthermore, recent papers suggest that children with A1 allele of this gene may receive less positive parenting, and that the effects of this gene on child symptoms may be moderated by parenting. We sought to replicate and extend these findings using behavioral measures in a nonclinical sample of young children. Methods: In a sample of 473 preschool-aged children and their mothers, structured clinical interview measures and maternal reports of child symptoms were collected, and standardized observations of parent-child interactions were conducted. Results: An association was detected between the DRD2 A1 allele and symptoms of depression and anxiety indexed using interview and parent report methods. As found in previous reports, children with the DRD2 A1 allele received less supportive parenting and displayed higher levels of negative emotionality during parent-child interactions. Tests of mediation and moderation were conducted. Conclusion: We found associations between the DRD2 A1 allele and early-emerging anxious and depressive symptoms in a community sample of preschool-aged children, and evidence of a gene-environment correlation and moderation of the main effect of child genotype on child symptoms by parenting. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
A SspI PCR-RFLP detecting a silent allele at the goat CSN2 locus
The comparison between the cDNA sequence obtained
and the published sequences of the goat CSN2 alleles
showed a new single nucleotide polymorphism (SNP)
(transition C-T) at the 180th nucleotide of the ninth exon.
This mutation, which took place at 124 nt from the
polyadenylation site, identifies a silent allele at the CSN2
locus named CSN2 A1.
Since the 9th exon C-T transition creates a SspI
endonuclease restriction site, the SspI digestion
of a PCR product of 360 bp spanning the 9th exon and
flanking regions, would allow carriers for the presence of
thymine to be identified.
The allelic frequency of the CSN2 A1 allele, determined
in 170 goats belonging to an undefined genetic type reared
in the province of Naples (Italy), was 0.23
It has been observed that the sequences
in the 3’ untranslated regions (UTR), proximal to the
polyadenylation site, can affect the mechanism of mRNA
deadenylation and degradation. Therefore, it is reasonable
to hypothesize that the C-T transition might, directly or
indirectly, influence the stability of the mRNA and,
consequently, the amount of protein produced
DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia
Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a clinical sample of 234 patients who were treated with antipsychotic drugs. Definite akathisia (a score ≥ 2 in the global clinical assessment of akathisia) was significantly less common in subjects who were prescribed SGAs (16.8%) than those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1- (thus, A2A2) patients. A1+ patients who were administered SGAs also had higher global clinical assessment of akathisia scores than the A1- subjects (p = 0.01). SGAs maintained their advantage over FGAs regarding akathisia, even in A1+ patients who were treated with SGAs. These results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs, and these variants may explain inconsistencies found across prior studies, when comparing FGAs and SGAs
Allelic and genotypic associations of DRD2 Taq I A polymorphism with heroin dependence in Spanish subjects: a case control study
Background: Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene ( DRD2) TaqI A polymorphism. Methods: We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients ( 207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects ( 98 males and 47 females). Results: The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls ( P = 0.011, odds ratio = 5.48, 95% CI 1.26-23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls ( 24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07-2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender ( odds ratio = 1.77, 95% CI 1.15-2.70). Conclusion: Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males
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