rs6277

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

A longitudinal prospective study of 338 young adult offspring from families at high and low risk for alcohol dependence examined predictors of cannabis use patterns and cannabis abuse/dependence from ages 8-30. A low P300 amplitude trajectory in childhood predicted cannabis abuse/dependence in males (P=0.01). A four-SNP ANKK1-DRD2 haplotype (rs4938012-rs4938015-rs1800497-rs6277, G-G-G-C) was significantly associated with cannabis use frequency patterns (P=0.0008). Among individuals with cannabis abuse/dependence, the CNR1 rs806368 A>G minor allele conferred a 5.4-fold increase in likelihood of frequent persistent use versus declining use (P=0.003, OR=5.4).

This review examines neurogenetic and neuropharmacological correlates of opioid use disorder (OUD) with emphasis on ancestry-specific genetic risk profiles. The paper identifies multiple genes involved in the reward pathway (DRD2, DRD3, DRD4, OPRM1, OPRK1, OPRD1, BDNF, NRXN3, COMT, SLC6A4, KCNC1, KCNG2) and their variants associated with OUD susceptibility and treatment response across different ethnic populations, highlighting critical research disparities where African Americans and Hispanics have been underrepresented in genetic association studies.

This double-blind, within-subject study examined 58 healthy non-smokers to investigate whether CHRNA4 rs1044396 and DRD2 rs6277 polymorphisms modulate nicotine's effects on visual distractor interference. DRD2 CC carriers showed the strongest reduction in distractor interference after 7 mg transdermal nicotine (F(2,49)=3.694, p=0.032), with a synergistic effect when combined with at least one CHRNA4 C allele, suggesting that dopaminergic and cholinergic genetic variations jointly influence individual responsiveness to nicotine's cognitive effects.

This genetic association study investigated whether ANKK1 Taq IA (rs18000497) and DRD2 C957T (rs6277) SNPs are associated with affective priming and facial expression recognition in 94 healthy Spanish volunteers. The C957T SNP TT genotype was significantly associated with stronger affective priming effects (F=10.653, P=0.002) and better recognition of angry facial expressions (F=11.980, P=0.001), while the Taq IA SNP showed no significant associations. The study suggests that affective priming and recognition of angry expressions are endophenotypes linking the ANKK1/DRD2 locus to emotional processing disorders.

This candidate gene association study examined 10 SNPs in addiction-related genes (CNR1, FAAH, DRD2, ANKK1, COMT, OPRM1) in university students and identified the FAAH C385A (rs324420) CC genotype as significantly associated with risky alcohol consumption (p=0.006, OR=2.38). The finding was replicated in an independent sample of 83 participants. Additionally, affective ratings of drug-related pictures were positively correlated with alcohol, tobacco, and cannabis consumption.

This study investigated whether 9 ANKK1 and 27 DRD2 SNPs predict haloperidol efficacy and tolerability in 88 acutely psychotic patients. rs2242592 in ANKK1 (p=0.008) and rs1124493 in DRD2 (p=0.001) were significantly associated with improved clinical response on PANSS scores. Three haplotype blocks (one in ANKK1, two in DRD2) were also associated with better clinical improvement. Results showed partial replication in the CATIE schizophrenia sample, with rs11604671 (in LD with rs2242592) associated with response, suggesting ANKK1 and DRD2 variability influences haloperidol response though further validation is needed.

Association study of 55 SNPs in 887 Hungarian adults examining genetic predisposition to aggression measured by the Buss-Perry Aggression Questionnaire. The HTR2A rs7322347 intronic variant showed significant association with aggression after Bonferroni correction (p = 0.0007), with carriers of the minor A allele showing lower aggression levels. The DRD4 rs916455 variant also showed nominal significance (p = 0.0275) but did not survive multiple testing correction.

A case-control study of 2,019 schizophrenia patients and 2,579 Japanese controls found the rs12807809-rs12278912 haplotype in the NRGN gene (chromosome 11q24.2) significantly associated with schizophrenia (global P = 0.0042). The TG haplotype was associated with increased risk (OR = 1.14, P = 0.0019), while the TA haplotype was protective (OR = 0.85, P = 0.0053). Gene expression analysis demonstrated the high-risk TG haplotype had significantly lower NRGN expression than the protective TA haplotype (P = 0.007 in HapMap samples, P = 0.002 in combined case-control samples).

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

A pharmacogenetic study of 446 schizophrenic patients (221 males, 225 females) from West Siberia investigating associations between 41 SNPs in dopaminergic genes and antipsychotic-induced hyperprolactinemia. The study found rs1799836 in MAOB gene associated with hyperprolactinemia in males (OR=0.748, p=0.048), and rs40184 and rs3863145 in SLC6A3 gene associated with hyperprolactinemia in the risperidone/paliperidone subgroup (OR=0.341, p=0.021 and OR=0.362, p=0.043, respectively), indicating protective effects.

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

A Hungarian doctoral dissertation examining psychogenetic endophenotypes through multiple candidate gene association studies. Investigated dopaminergic and serotonergic polymorphisms (DRD2, DRD4, COMT, GDNF, HTR1A, HTR1B, SLC6A4) in relation to personality dimensions (impulsivity, anxiety, depression), flow susceptibility, hypnotizability, cognitive reaction time, and longevity. Key findings include associations between GDNF rs3812047 and rs3096140 with anxiety measures (p=0.0007, p=0.0014), COMT Val158Met with hypnotizability, and DRD4 VNTR 7-repeat with reaction time.

This Hungarian dissertation examined psychogenetic endophenotypes in healthy young adults (N~1800+), investigating associations between dopaminergic and serotonergic genetic polymorphisms and psychological traits including impulsivity, mood dimensions, flow susceptibility, hypnotizability, and cognitive performance. Key findings included significant associations between DRD4 VNTR 7-repeat allele and lower impulsivity (p=0.006), COMT Val/Met (rs4680) and impulse control (p=0.047), HTR1B 1997 AG (rs13212041) and impulsivity (p=0.003-0.004), GDNF variants and anxiety, and notably, a population frequency increase in DRD4 7-repeat allele carriers with advancing age suggesting possible survival advantage.

This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.

Case-control study of 881 smokers (219 abstinent, 662 not abstinent at one year) examining dopamine pathway variants on smoking cessation. DRD2 TaqIA (rs1800497) was significantly associated with smoking abstinence (p=0.01), with minor allele carriers being less likely to quit (OR: 0.47, 95% CI: 0.24-0.94). Other DRD2 variants and SLC6A3 VNTR were not significantly associated with cessation.

This is a comprehensive literature review of candidate genes and their single nucleotide variants associated with antipsychotic-induced tardive dyskinesia in schizophrenia patients. The review examined genes involved in dopamine system (DRD1, DRD2, DRD3), catecholamine metabolism (COMT), serotonin system (HTR2A, HTR2C), and other pharmacodynamic and pharmacokinetic pathways. Timely identification of genetic variants in these genes could contribute to developing diagnostic tests and selecting safer antipsychotic therapy.

Case-control genetic association study of 127 Vietnam war veterans with PTSD and 228 controls found that the DRD2 957C>T polymorphism (rs6277) is significantly associated with PTSD susceptibility. The C allele was more frequent in PTSD cases (51.7%) vs controls (42.5%, P=0.021, OR=1.45). The CC genotype showed twice the odds of PTSD compared to TT (P=0.041), with 14% of PTSD susceptibility attributable to this genotype.

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Study of 1,723 participants from the Polyp Prevention Trial examined associations between dopamine D2 receptor (DRD2) polymorphisms and colorectal adenoma recurrence. DRD2 rs1799732 CT genotype was associated with increased risk of any adenoma recurrence (OR: 1.30; 95% CI: 1.01-1.69), while rs1800497 TT genotype was associated with advanced adenoma recurrence (OR: 2.40; 95% CI: 1.11-5.20). Dietary components including alcohol and fat intake varied significantly across DRD2 genotypes.

This study investigated whether HTR2A A-1438G/T102C polymorphisms (rs6311/rs6313) predict aripiprazole treatment response in 128 Han Chinese schizophrenia patients. The GG/CC genotype group predicted poor negative symptom response (PANSS negative score 3.93 points higher in GG/CC vs. AA/TT, P=0.007), with clinical factors like medication dosage and age also significantly influencing treatment outcomes.

A pharmacogenetic association study of 446 schizophrenia patients from West Siberia examined 41 SNPs in dopamine pathway genes (DRD1, DRD2, DRD3, DRD4, SLC6A3, MAOA, MAOB) for association with antipsychotic-induced hyperprolactinemia (HPRL). rs1799836 in MAOB showed significant protective association with HPRL in men (OR=0.748, p=0.048), while rs40184 (OR=0.341, p=0.021) and rs3863145 (OR=0.362, p=0.043) in SLC6A3 showed protective effects specifically in risperidone/paliperidone-treated patients.

Literature review of 77 publications examining the effects of genes COMT, MAO-A, MAO-B, DAT, DRD2, VMAT2, TPH2, and SNCA on Parkinson's disease neuropsychiatric symptoms and therapy response. Key polymorphisms include rs1800497 (DRD2) associated with impulse control disorders, rs6269/rs4633/rs4818/rs4680 (COMT) with cognitive decline, and rs1352250/rs6582078 (TPH2) with impulse control. The review identifies genetic predictors for early complications (cognitive decline, depression, psychosis, impulse control disorders) and therapy optimization, relevant for patient selection for deep brain stimulation.

Haplotype-tagging SNP analysis in 364 individuals from 152 ADHD families identified significant associations between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596) and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are valid ADHD endophenotypes linked to dopaminergic and noradrenergic pathways.