Allele Appears Protective Against Alcohol Use

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.