FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence

Ann Hum Genet. 2020 May;84(3):259-270. doi: 10.1111/ahg.12368. Epub 2019 Dec 2.

Abstract

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2-fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332-2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH-dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171-2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404-2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444-2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.

Keywords: FAAH; genetic susceptibility; methamphetamine dependents; single-nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amidohydrolases / blood
  • Amidohydrolases / genetics*
  • Amphetamine-Related Disorders / genetics*
  • Asian People / genetics
  • Case-Control Studies
  • China
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Methamphetamine*
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Methamphetamine
  • Amidohydrolases
  • fatty-acid amide hydrolase