rs1800497

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.

This study demonstrates a significant gene-gene interaction between the obesity-risk FTO rs8050136 polymorphism and the dopamine D2 receptor ANKK1/TaqIA rs1800497 polymorphism affecting body composition and insulin sensitivity. Among 2245 participants from the Tübingen Family study and 2921 from the Malmö Diet and Cancer study, the FTO variant was associated with increased body fat (β 0.056±0.016) and waist circumference (β 0.017±0.008) and reduced insulin sensitivity (β -0.121±0.037) only in carriers of the ANKK1 T risk allele; no associations were found in ANKK1 C allele homozygotes. Brain fMRI imaging in 45 participants also showed the interaction on central insulin sensitivity in the caudate nucleus.

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 pharmacogenetic study in 61 first-episode schizophrenia patients found that GRM3 rs1468412 TT genotype was associated with worsening spatial working memory performance after antipsychotic treatment (p=0.001, Cohen's d=0.75), while GRM3 rs6465084 AA genotype was associated with improved negative symptoms after treatment (p=0.046). No significant associations were found between COMT Val158Met or DRD2/ANKK1 variants and cognitive or symptom changes.

This review examines the genetic and epigenetic basis of Tourette Syndrome (TS), a neurodevelopmental disorder with high heritability (0.45-0.77). The paper reviews candidate gene associations including variants in SLITRK1 (rs9593835, rs9546538, rs9531520), DRD2/ANKK1 (rs1800497), ADORA1/ADORA2A (rs2228079, rs5751876), and other dopaminergic genes, along with a large GWAS in 1285 cases and 4964 controls highlighting rs7868992 in COL27A1. The review proposes that epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) may link genetic susceptibility with environmental factors in TS pathogenesis.

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.

Association study of 446 Russian schizophrenia patients examining the functional ANKK1 rs2734849 polymorphism and antipsychotic-induced hyperprolactinemia (HPRL). The C allele was significantly associated with higher HPRL risk (OR=1.30, p=0.05 in total group; OR=1.49, p=0.04 in females), while the T allele was protective. This variant likely affects DRD2 expression through NFκB signaling, influencing D2 receptor density on pituitary lactotrophs.

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

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.

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.

An Italian preliminary study of 32 female patients with eating disorders (25 anorexia nervosa, 5 bulimia nervosa, 2 binge eating disorder) investigated the association between dopaminergic system polymorphisms (DRD2, DRD4, COMT, DAT) and body image disturbance. While high body image disturbance was confirmed in patients, the study found no statistically significant differences in polymorphism distributions between diagnostic groups. A significant association was found only for the DAT 10R/10R genotype (χ²=21.57; p=0.006 for DRD4) with increased body dissatisfaction scores in specific body regions, but overall the preliminary results did not support the hypothesis of shared Reward Deficiency Syndrome polymorphisms with addiction disorders.

This review comprehensively summarizes the latest genetic studies on schizophrenia, including family studies (heritability ~80%), genome-wide association studies, epigenetic mechanisms, candidate gene investigations, and next-generation sequencing findings. Key GWAS findings identified 108 schizophrenia-associated loci including variants in MIR137 (rs1625579), TCF4 (rs12966547), CSMD1 (rs10503253), CACNA1C (rs4765905), ANK3 (rs10761482), and MHC region variants, with evidence for polygenetic inheritance involving both common SNPs and rare copy number variations.

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 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.

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 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 meta-analysis of six European populations (N=1,641, mean age 82 years) investigating genetic associations with delirium in elderly patients. The SLC6A3 rs393795 AA genotype showed protective association with delirium (OR=0.37-0.4, 95% CI 0.2-0.6, P=0.0003), while DRD2 rs6276 GG genotype showed borderline protective effect especially in patients with cognitive impairment (OR=0.6, 95% CI 0.4-1.0, P=0.06). SLC6A3 rs1042098 showed no significant association.

Meta-analytic review of candidate gene studies for childhood ADHD examining 19 genes. Significant associations identified for DAT1 (3' UTR VNTR: OR=1.12, p=0.028; rs27072: OR=1.20, p=0.006), DRD4 (exon 3 VNTR: OR=1.33, p=0.00007; rs1800955: OR=1.21, p=0.007), DRD5, 5HTT, HTR1B (rs6296: OR=1.11, p=0.010), and SNAP25 (rs3746544: OR=1.15, p=0.030).

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 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.

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.

This pharmacogenetic study examined determinants of non-ergoline dopamine agonist discontinuation in 90 Parkinson's disease patients. Non-genetic factors associated with discontinuation included apomorphine use (HR 6.26) and levodopa dosages 500-1000 mg (HR 2.31). In the genetic subgroup (n=38), the absence of a 15× DRD2 CA repeat allele was significantly associated with decreased discontinuation (HR 0.23; 95% CI 0.07-0.81), while DRD3 Msp I polymorphism showed a suggestive allele dose effect.

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.

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.

A case-control study (N=99: 49 patients with major depressive disorder, 50 controls) conducted in Mexican mestizo population analyzing 8 genetic variants in serotonin and dopamine receptors (HTR1A rs6295, HTR2A rs6311/rs6313/rs6314, HTR6 rs1805054, DRD2 rs1801028/rs1800497, DRD3 rs6280) using PCR-RFLP genotyping. The study characterized genotype and allele frequencies in depressed patients versus healthy controls and evaluated associations with antidepressant treatment response using Hamilton Depression Scale.

This case-control association study examined five DRD2 polymorphisms in 213 schizophrenia patients and 196 controls from South India. H313H TT genotype was significantly associated with schizophrenia (P=0.004) and with better antipsychotic treatment response, while TaqIA A1A1 genotype was protective (P=0.029). DRD2 variants showed distinct associations with specific symptoms and treatment outcomes, highlighting ethnic and cultural factors in disease manifestation and antipsychotic response.

This study identifies and characterizes ANKK1 (ankyrin repeat and kinase domain containing 1), a novel serine/threonine kinase gene located downstream of DRD2 on chromosome 11q23.1. The functionally significant Taq1A polymorphism (rs1800497, g.32806C>T) previously associated with addiction traits is shown to cause an amino acid substitution (p.Glu713Lys) within the 11th ankyrin repeat of ANKK1 rather than directly affecting DRD2, suggesting that ANKK1 activity changes may explain addiction-related associations previously attributed to DRD2 variation.