rs324420

rs324420 is a single nucleotide polymorphism in the fatty acid amide hydrolase (FAAH) gene, commonly referred to as C385A or Pro129Thr (P129T). The reference allele is C and the variant allele is A, which changes an amino acid in the FAAH enzyme from proline to threonine at position 129.

Functionally, the A allele reduces FAAH enzymatic activity, leading to higher steady-state levels of the endocannabinoid anandamide and related N-acylethanolamines. This alteration in endocannabinoid signaling can influence neural circuits involved in pain, emotion, and reward.

Associations observed in human studies have spanned several domains. In pain research, some studies report reduced pain sensitivity or altered pain processing in A allele carriers, though findings are not uniform across populations. In fear conditioning and extinction, there is evidence that A carriers may show differences in extinction learning or recall, with results varying by study design and sample size. Research on anxiety traits, stress responses, and susceptibility to certain substance use disorders has yielded mixed results, with small effect sizes and inconsistent replication. Some investigations have also explored links to metabolic traits such as body mass index, but findings are again heterogeneous.

Frequency of the A allele varies across populations, reflecting broader human genetic diversity. rs324420 remains a widely studied functional variant in the endocannabinoid system, often examined in candidate-gene and association studies. However, effect sizes are typically modest, and replication across cohorts is not universal. It is not used as a clinical diagnostic marker, and findings should be interpreted with caution.