Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns

Bjerregaard, Peter; Mikkelsen, Stine Schou; Becker, Ulrik; Hansen, Torben; Tolstrup, Janne S

doi:10.1016/j.drugalcdep.2014.09.774

Cited by 14 publications

(10 citation statements)

References 35 publications

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“…It has been suggested that an altered conversion rate of alcohol that leads to the excess build-up of acetaldehyde, and hence a more severe response to alcohol, could reduce heavy alcohol use and related diseases ( 42 ). However, Bjerregaard and colleagues did not confirm the presence of the Asian genotype pattern in a study on the genetic variation in alcohol-metabolizing enzymes among Inuit ( 43 ). Yet, AST may reflect alcohol consumption ( 41 , 44 ) and we found an increase in AST with increased reported alcohol consumption.…”

Section: Discussionmentioning

confidence: 95%

Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

Rex

Krarup

Laurberg

et al. 2016

International Journal of Circumpolar Health

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Background. Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. Objective. We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Design and methods. Population-based investigation of Inuit (n 0441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n 0136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Results. Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p 00.035). Alcohol intake was associated with AST (p B0.001) and GGT (p 00.001), and HBV infection was associated with ALP (p 00.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p B0.001), GGT (p B0.001) and ALP (p 00.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry. Conclusions. Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect of alcohol intake on AST. HBV infection was slightly associated with ALP but not with other liver biochemistry parameters.

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Section: Discussionmentioning

confidence: 95%

Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

Rex

Krarup

Laurberg

et al. 2016

International Journal of Circumpolar Health

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“…Based on the well-known genetically determined pattern of alcohol metabolisation among certain Asian peoples, the Asian origin of Inuit, and the perceived high prevalence of alcohol-related problems it has been speculated, mostly by non-professionals, that the drinking pattern of the Inuit might be genetically determined in spite of the fact that the above mentioned Asian genetic pattern normally would reduce the risk of alcoholism. However, studies among Alaska Natives, Siberian Eskimos, Chuckchi, and Greenlanders showed an absence of the protective Asian genotype pattern that included an inactive ALDH2 [46][47][48][49]. In a study of 4162 Inuit from Greenland [47] a remarkable result was a low prevalence of an ALDH1B1 TT genotype among Inuit which was associated with a low odds ratio for heavy drinking, positive CAGE, and binge drinking.…”

Section: Discussionmentioning

confidence: 99%

“…However, studies among Alaska Natives, Siberian Eskimos, Chuckchi, and Greenlanders showed an absence of the protective Asian genotype pattern that included an inactive ALDH2 [ 46 – 49 ]. In a study of 4162 Inuit from Greenland [ 47 ] a remarkable result was a low prevalence of an ALDH1B1 TT genotype among Inuit which was associated with a low odds ratio for heavy drinking, positive CAGE, and binge drinking. On the other hand, the ADH1C GG genotype of the Inuit was directly associated with heavy drinking and with a positive CAGE test for alcoholism [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Alcohol in Greenland 1950-2018: consumption, drinking patterns, and consequences

Bjerregaard

Larsen

Sørensen

et al. 2020

International Journal of Circumpolar Health

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Alcohol is the single most important public health challenge in Greenland. We provide an overview of alcohol consumption, drinking patterns, and consequences of excessive use of alcohol in Greenland since 1950 through a synthesis of published results and analyses of population-based interview surveys. The import of alcohol fluctuated over the last 70 years with a peak in the 1980s at 22 litres 100% alcohol per person per year. In 1950 and 2015, the import of alcohol was similar at 8 litres. Several explanations have been put forward to explain the changes including restrictions, increased tax, demographic changes, treatment of alcohol disorders, and public health interventions. The proportion of abstainers increased from 1993 to 2018 while the proportion of participants with regular consumption decreased. About half of the population reported binge drinking at least monthly. Compared with Denmark, there were more abstainers and binge drinkers in Greenland, and fewer had a regular consumption. Although genetics may play a role for drinking patterns, social and cultural conditions are more important. Exposure to domestic alcohol problems and sexual abuse in childhood parallel the recorded import of alcohol and is a likely cause of transgenerational consequences such as youth suicides and alcohol problems.

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“…Eligibility criterion was Danish citizenship, and the participants does not reflect the ethnic admixture of Copenhagen (for instance, the proportion of inhabitants with foreign citizenship was 8% in 1994). However, even a few participants of foreign ethnicity could confound our results since the ADH1B*2 allele has shown considerable population stratification [ 25 ]. Hence, information on birth place as recorded in the Danish Civil Registration System [ 26 ] was obtained, and participants who were born in Asia, Africa, the Middle East, South America, and Greenland were excluded (n=243).…”

Section: Methodsmentioning

confidence: 99%

Alcohol Intake and Risk of Ischemic and Haemorrhagic Stroke: Results from a Mendelian Randomisation Study

2018

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Background and PurposeTo test whether alcohol intake, both observational and estimated by genetic instruments, is associated with risk of ischemic and haemorrhagic stroke. MethodsWe used data from the Copenhagen City Heart Study 1991 to 1994 and 2001 to 2003, and the Copenhagen General Population Study 2003 to 2012 (n=78,546). As measure of alcohol exposure, self-reported consumption and genetic variation in alcohol metabolizing genes (alcohol dehydrogenase ADH1B and ADH1C) as instrumental variables were used. Stroke diagnoses were obtained from a validated hospital register. ResultsDuring follow-up 2,535 cases of ischemic and haemorrhagic stroke occurred. Low and moderate alcohol intake (1 to 20 drinks/week) was associated with reduced risk of stroke. The hazard ratios associated with drinking 1 to 6, 7 to 13, and 14 to 20 drinks/week were 0.84 (95% confidence interval [CI], 0.76 to 0.92), 0.83 (95% CI, 0.73 to 0.94), and 0.84 (95% CI, 0.73 to 0.97), respectively, compared with drinking <1 drink/day. ADH1B and ADH1C genotypes were not associated with risk of stroke. Further analysis to test the included measures revealed that increasing alcohol intake (per 1 drink/day) was positively associated with risk of alcoholic liver cirrhosis, but not associated with risk of stroke, and that increasing blood pressure (per systolic 10 mm Hg) was not associated with risk of alcoholic liver cirrhosis, but positively associated with risk of stroke. Conclusions Low and moderate self-reported alcohol intake was associated with reduced risk of stroke. The result was not supported by the result from the causal genetic analysis.

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Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns

Cited by 14 publications

References 35 publications

Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

Alcohol in Greenland 1950-2018: consumption, drinking patterns, and consequences

Alcohol Intake and Risk of Ischemic and Haemorrhagic Stroke: Results from a Mendelian Randomisation Study

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