rs740603

Case-control study of 604 Han Chinese examining associations between two COMT gene polymorphisms (rs740603 and rs4818) and schizophrenia. Found no significant association with schizophrenia susceptibility, but rs740603 and the rs740603(G)-rs4818(G) haplotype were associated with negative symptoms severity, particularly in females (p=0.025 for rs740603; p=0.021 for haplotype in females).

This population-based study of 3,904 subjects examined the interaction between COMT and TXNRD2 SNPs and temporomandibular disorder (TMD) pain, modified by depressive symptoms. Six SNPs from the first COMT/TXNRD2 haploblock showed significant interactions with depressive symptoms (smallest p-value: 2.7 × 10^-10), with opposite SNP effects between depressed and non-depressed individuals. In non-depressed subjects, rs5993882 (COMT) was most associated with TMD pain, while in depressed subjects, rs1544325 (COMT) and TXNRD2 SNPs were preferentially associated. The findings indicate that COMT polymorphisms affect pain perception through a mechanism significantly moderated by depressive symptoms.

This association study examines COMT polymorphisms and cocaine-induced paranoia (CIP) in European-American and African-American populations. The nonsynonymous Val158Met variant (rs4680) and three additional SNPs (rs933271, rs5993883, rs740603) were identified as potentially functional. Family-based and case-control analyses revealed significant haplotype associations with CIP, particularly haplotype A-A-T in both European-American families and unrelated African-American individuals, supporting COMT's role in dopamine/norepinephrine metabolism affecting cocaine-induced psychiatric symptoms.

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 study investigated 12 genetic polymorphisms in four dopamine-related genes (COMT, MAOA, MAOB, and DBH) in 179 incarcerated male Russian adolescents and 242 matched controls to identify genetic associations with aggressive behavior and conduct disorder. The authors found that while individual genetic variants did not differentiate groups, specific combinations of variants (haplotypes) and interactions between variants within and across genes produced informative classifications for incarceration status (P < 0.0001, Nagelkerke R² = 0.141) and conduct disorder diagnosis (P < 0.0001, Nagelkerke R² = 0.158), with a 4-marker model involving COMT rs737865, COMT rs165599, DBH rs1611115, and DBH rs739398 being most predictive.

This case-control association study of 931 Caucasian schizophrenia patients (270 with treatment-resistant schizophrenia [TRS], 661 non-TRS) examined COMT rs4680 (Val158Met) and rs4818 polymorphisms for sex-specific associations with treatment resistance. In females with TRS, the COMT rs4680 AA genotype was nominally more frequent than G carriers (p=0.033), and the COMT rs4818 CC genotype was significantly more frequent than G carriers (p=0.014). The high-activity G-G/G-G haplotype was protective against TRS in females (p=0.009, OR=2.10 for non-carriers vs GG carriers), but no associations were found in males. Results suggest estrogen-modulated, sex-specific effects of COMT variants on antipsychotic treatment response.

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 case-control association study of 650 German migraine with aura (MA) patients and 650 controls tested 53 variants across 10 dopaminergic system genes. Three SNPs in the dopamine-beta hydroxylase (DBH), dopamine transporter (SLC6A3), and dopamine D2 receptor (DRD2) genes showed significant associations with MA. After gene-wide correction, rs2097629 in DBH (OR=0.77, p=0.0012) and rs40184 in SLC6A3 (OR=0.81, p=0.0082) remained significant, with supporting evidence from 2,937 British controls. These findings provide genetic evidence for dopaminergic system involvement in MA pathogenesis.

This family-based association study investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for sexually dimorphic genetic effects in 474 ADHD-affected offspring. The Met allele of COMT Val158Met showed stronger association in males (OR=1.42, p=0.003) but not females (p=0.936), and when combined with prior data showed significant gender effects (p=0.007). SLC6A2 and MAOA also showed sex-stratified associations, supporting the hypothesis that ADHD risk genes have sexually dimorphic effects.

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.