rs6280

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 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 international doctoral thesis examined gene-physical activity interactions in fibromyalgia through six studies analyzing 64 SNPs across 34 candidate genes in Spanish women. The case-control study (314 fibromyalgia cases vs. 112 controls) identified associations of rs841 (GCH1), rs1799971 (OPRM1), and rs2097903 (COMT) with fibromyalgia susceptibility (p=0.04, p=0.02, and p=0.04 respectively). Cross-sectional studies (n=274-276 fibromyalgia patients) found that SCN9A rs4453709 and other genetic polymorphisms interacted with physical activity to influence pain, fatigue, and resilience outcomes.

This paper presents CalPen, a web-based tool for calculating penetrance (disease likelihood given a mutation) in complex genetic disorders. The authors validated CalPen against published penetrance calculations for schizophrenia-associated copy number variants (CNVs) and single nucleotide polymorphisms (SNPs). They analyzed 15 CNVs in 39,059 schizophrenia patients and 55,084 controls (average penetrance 7%, ranging from ~1.4% for 15q11.2 deletions to ~20% for 22q11.21 CNVs) and 145 SNPs in 45,405 patients and 122,761 controls (average penetrance 0.7%, with rs1801028 showing the highest at 1.6%).

A case-control association study of 1,237 Pakistani subjects (479 with major depression, 222 with bipolar disorder, 146 with schizophrenia, 390 controls) examined 11 dopaminergic system gene variants. Significant risk associations were found for rs1006737 and rs2238056 (CACNA1c) with bipolar disorder (OR=1.14-1.15), while rs10033951 (DRD5), rs2388334 (POU3F2), and the DRD4 120bp VNTR showed protective effects across disorders (OR=0.81-0.86).

This candidate gene study identified four SNPs in the DRD3 (dopamine D3 receptor) gene associated with reduced risk for posttraumatic stress disorder (PTSD) in a discovery sample of 491 white non-Hispanic trauma-exposed veterans and partners (rs2134655, rs201252087, rs4646996, and rs9868039; odds ratios 0.59-0.69; corrected p-values 0.005-0.049). In a replication sample of 601 trauma-exposed African Americans, rs2251177, located 149 bp from the top discovery SNP, showed nominal association with PTSD in men (OR=0.32, uncorrected p=0.01). The protective alleles suggest DRD3 dysfunction may mediate PTSD through effects on executive functioning and emotional reactivity.

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 pilot association study examining single nucleotide variants rs6280 in DRD3 and rs9652490 in LINGO1 genes and their association with levodopa-induced dyskinesias (drug dyskinesia) in Parkinson's disease patients from Yakutia, Russia. The study of 47 PD patients (7 with dyskinesias, 40 without) found no statistically significant association between either SNV and drug dyskinesia development (p > 0.05), though longer levodopa therapy duration and higher equivalent daily levodopa doses were significantly associated with dyskinesia risk.

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.

This comprehensive review examines the pharmacogenetics of antipsychotic drug treatment, synthesizing evidence on how genetic variations influence both treatment efficacy and adverse effects. Key findings show dopamine receptor genes (DRD2, DRD3) predominantly associated with positive symptom response, while serotonin genes (HTR1A, HTR2A, HTR2C) associate with negative symptom improvement. For weight gain, the HTR2C promoter polymorphism (-759 C/T) shows strong protective effects (relative risk 3.45) in risperidone/olanzapine treatment. Tardive dyskinesia associations involve multiple genes including DRD2, DRD3, HTR2A, HTR2C, and SOD2, though GWAS findings often diverge from candidate gene results.

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.

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.

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 meta-analysis of 794 schizophrenia cases and 1,078 controls from three European populations identified a common protective DRD3 haplotype against schizophrenia (Mantel-Haenszel χ² p-value = 0.00227; OR = 0.79, 95% CI 0.68-0.92). The protective haplotype has reached high frequency in non-African populations through positive selection acting on the non-synonymous SNP rs6280 (Ser9Gly), suggesting natural selection influences susceptibility allele frequencies in psychiatric disorders.

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.

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.

A functional polymorphism rs6280 in the DRD3 gene (dopamine D3 receptor) was found to be significantly associated with nicotine dependence in European-American smokers. The study examined the relationship between this SNP and smoking phenotypes in the study population.

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.

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 doctoral thesis conducted multiple candidate gene association studies in 274-426 southern Spanish women with fibromyalgia to investigate gene-physical activity/sedentary behavior interactions with pain, fatigue, and resilience. Study III identified rs841 (GCH1) GG genotype (OR=0.61, p=0.04) and rs2097903 (COMT) AT/TT genotypes (OR=1.66, p=0.04) associated with fibromyalgia susceptibility, and confirmed rs1799971 (OPRM1) GG genotype (OR=0.58, p=0.02) confers genetic risk. Study IV found rs6311/rs6313 (HTR2A) polymorphisms individually associated with algometer pain score, and gene-sedentary behavior interactions involving rs4680/rs165599 (COMT), rs1383914 (ADRA1A), rs12994338/rs4453709 (SCN9A), and rs6860 (CHMP1A) significantly associated with pain outcomes. SCN9A emerged as most robust gene for fibromyalgia phenotype.