rs9332377

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 candidate gene association study examined 14 SNPs in ADRB2 and COMT genes in 1,004 Western Australian adolescents (age 17) to identify genetic variants associated with chronic musculoskeletal complaints. Of the SNPs tested, only rs2053044 in ADRB2 (recessive model) showed association with chronic disabling neck and low back pain (OR = 2.49; 95% CI = 1.25-4.98; p = 0.01) and pain in 3-4 body areas (OR = 1.86; 95% CI = 1.13-3.06; p = 0.02). The findings suggest that genetic variants in ADRB2 may be involved in regulating chronic musculoskeletal pain in adolescents.

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 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.