Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption

Abstract

The functional polymorphism Asn(107) Ile (rs324981, A > T) of the neuropeptide S receptor (NPSR1) gene is involved in the modulation of traits that affect alcohol use. Hence, we have examined whether the NPSR1 A/T polymorphism is associated with alcohol use disorders (AUD) and alcohol use in a population-representative sample. Lifetime AUD were assessed by the MINI psychiatric interview (n = 501) in the older cohort of the longitudinal Estonian Children Personality Behaviour and Health Study at age 25. Alcohol use, environmental adversities and personality were reported by both the younger (original n = 583) and the older cohort (original n = 593) in three study waves. NPSR1 associations with AUD and alcohol use differed by sex. In females, both AUD [odds ratio (OR) = 7.20 (0.94-55.0), P = 0.029] and harmful alcohol use were more prevalent in A-allele carriers. In contrast, in males, AUD was more frequent in T-allele carriers [OR = 2.75 (1.19-6.36), P = 0.017], especially if exposed to adverse environments at age 15 [OR = 10 (1.18-84.51), P = 0.019]. Alcohol use was higher in male T-allele carriers at ages 15 and 18 as well. Similarly to females, however, the risk allele for higher alcohol use for males at age 25 was the A-allele. Many of the effects on alcohol use were explained by genotype effects on measures of personality. In the general population, the NPSR1 Asn(107) Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age. The results are in line with the impulsivity and personality regulating role of the NPSR1.

Emerging targets for addiction neuropharmacology

“…For instance, it is now known that in humans, NPSR is present in two isoforms deriving from a A>T single nucleotide polymorphism, resulting in an Asn107Ile exchange, which confers ten-fold higher potency to the NPSR107Ile isoform (Reinscheid et al, 2005). This isoform of NPSR is associated with impulsivity, stress-sensitivity and alcohol use disorder (Laas et al, 2014; Laas et al, 2015), which is in line with preclinical data indicating that overfunction of the system may be linked to enhanced relapse propensity (Cannella et al, 2009a; Paneda et al, 2009; Kallupi et al, 2010). …”

Activation of Hypocretin-1/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S

“…T single nucleotide polymorphism, resulting in an Asn 107 Ile exchange, with NPS showing a tenfold higher potency on the NPSR 107 Ile isoform (51). NPSR 107 Ile was associated with impulsivity, stress sensitivity, hyperactivity, neuroticism, and, most importantly, alcohol use disorders (52,53). Although alcohol-cue reactivity in NPSR 107 Ile-carrying alcoholics had not been studied yet, one study associated NPSR 107 Ile with overinterpretation and overreaction to fear-conditioned stimuli (54).…”

Relapse of drunk driving and association with traffic accidents, alcohol-related problems and biomarkers of impulsivity

“…Another, recent candidate for regulation of impulse control and alcohol use is the neuropeptide S (NPS) system (36) that in turn can stimulate dopaminergic neurotransmission (37). Much of this research has been carried out in animals, but in humans, a functional polymorphism of the gene that encodes for the neuropeptide S receptor 1 (NPSR1) (38) has been associated with the development of personality, hyperactivity, alcohol use and alcohol use disorders (39)(40)(41)(42). NPSR1 gene carries a functional A/T single-nucleotide polymorphism (SNP, rs324981) coding for an Asn-Ile exchange at position 107.…”