rs1799971

This study identified rare genetic variants in the opioid receptor genes OPRK1 and OPRM1 as susceptibility factors for Tourette syndrome in a French cohort of 120 patients. Exome sequencing combined with hypothesis-driven candidate gene screening revealed an excess of rare variants in OPRK1 (4.2% in cases vs 0.5-0.8% in controls, p=0.003) and a weaker association with OPRM1 (6.7% in cases vs 2.3% in controls, p=0.048). Functional studies in zebrafish demonstrated that oprk1 knockdown affects motor activity during early development, supporting a role for opioid receptor dysfunction in tic pathogenesis.

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 develops and compares two microarray-based genotyping methods (ASO and ASA) for three ADHD-related SNPs: rs1800544 (ADRA2A), rs5569 (SL6CA2), and rs1799971 (OPRM1). The ASA approach demonstrated superior performance with 100% accuracy, shorter analysis time (3 hours), and lower DNA requirement (4 ng) compared to ASO. Both methods enable rapid, cost-effective pharmacogenetic testing suitable for decentralized clinical laboratories.

A qualitative literature review of state-of-the-art behavioral and pharmacological treatments for alcohol use disorder (AUD). The review summarizes evidence-based psychosocial treatments (cognitive behavioral therapy, motivational interviewing, behavioral couples therapy) and pharmacological interventions (naltrexone, acamprosate, Vivitrol), with emphasis on relapse prevention. The paper discusses precision medicine approaches, including examination of the OPRM1 Asn40Asp polymorphism (SNP) as a potential predictor of naltrexone response, though recent evidence questions its effectiveness as a biomarker.

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.

The Acute to Chronic Pain Signatures (A2CPS) is a multicenter prospective observational study protocol designed to identify biomarkers and biosignatures that predict development of chronic postsurgical pain. The study will recruit 3,600 patients undergoing knee arthroplasty or thoracic surgery and collect comprehensive biopsychosocial assessments including genetic variants via the Infinium Global Screening Array (GSA BeadChip with >650,000 markers), brain imaging, quantitative sensory testing, proteomic/metabolomic analyses, and patient-reported outcomes at baseline, 6 weeks, 3 months, and 6 months to identify predictive biomarkers for the transition from acute to chronic pain.

This review examines polymorphisms in six genes (SCN9A, KCNS1, GCH1, COMT, OPRM1, OPRK1) involved in nociception and their associations with chronic post-surgical pain (CPSP). Key findings include rs4680 in COMT associated with higher pain risk (OR 3.42 in knee replacement patients), rs734784 in KCNS1 explaining ~5% of pain variance in lumbar discectomy patients, and rs6746030 in SCN9A conferring increased pain sensitivity. The paper reviews conflicting evidence across multiple surgical populations and discusses potential clinical applications of genetic testing for CPSP risk stratification.

This pharmacogenetic analysis of the COMBINE Study (n=604 white participants) evaluated the OPRM1 Asn40Asp polymorphism as a predictor of naltrexone response in alcohol-dependent individuals. Individuals carrying the Asp40 allele who received naltrexone monotherapy (without cognitive behavioral intervention) showed significantly improved outcomes: 87.1% achieved good clinical outcomes compared to 54.8% of Asn40 homozygotes (OR=5.75, 95% CI 1.88-17.54, p=0.005). The Asp40 allele carriers showed increased abstinence days and decreased heavy drinking days with naltrexone but not placebo, while Asn40 homozygotes responded equally to both treatments.

Population genetics study of OPRM1 and COMT gene variants in the Chaco province of Argentina. Genotyped 11 SNPs in 54 individuals from Misión Nueva Pompeya and compared with published data from Resistencia (n=109) and Wichí native communities (n=27). Found significant population differentiation at Fst values ranging from 1.507% to 2.744% between populations, with notable variation in pain-related and dopaminergic genes that could inform personalized pain management strategies.

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.