Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns
Introduction
Alcohol related somatic, psychiatric and social consequences are major public health problems in many indigenous populations, including the Inuit in Greenland. In Greenland, the average yearly consumption of alcohol has for the last 20 years been equivalent to 12 l of pure alcohol per person aged 15 and above (Statistics Greenland, 2013) but binge drinking is prevalent (Jeppesen and Larsen, 2008).
Alcohol is metabolized by two isoenzymes, i.e., alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), coded from different gene loci (Hempel et al., 1984, Yoshida et al., 1984, Bosron and Li, 1986, Eriksson et al., 2001). Variations in alcohol metabolizing enzymes have been associated with a higher frequency of alcohol problems (Tolstrup et al., 2008), higher prevalence of binge drinking (drinking five drinks or more per occasion (Husemoen et al., 2008)) and alcohol-induced hypersensitivity (Linneberg et al., 2010). In East Asians, an allele of ALDH encoding inactive acetaldehyde dehydrogenase is prevalent. Carriers of this allele experience malaise and flushing when drinking, and it has consistently been shown that such individuals binge-drink less often and have lower risk of alcoholism compared with individuals with functional ALDH (Harada et al., 1982, Higuchi et al., 1994, Higuchi et al., 1996, Muramatsu et al., 1995, Luczak et al., 2006, Zintzaras et al., 2006). This allele has not been observed in a general white population (Tolstrup et al., 2008), but it is unknown if it exists in Inuit. However, neither typical nor atypical flushing has been reported from Greenland.
The ancestors of the Inuit migrated from Siberia to Alaska as late as 2000 years ago and arrived in Greenland from arctic Canada within the last millennium (Gulløv, 2004, Reich et al., 2012). The distribution of the genetic variations in ADH and ALDH among Inuit and related indigenous populations of Alaska and Siberia is largely unknown. Among Alaska Natives entering treatment for alcoholism the allele distributions of ADH and ALDH were similar to those of a general sample of Yupik Eskimos, and not significantly different among seven indigenous populations in the study. The distribution of alleles did not resemble the typical Asian distribution (Segal, 1999). Other studies showed that the inactive ALDH2 allele was absent among Alaska Natives, Siberian Eskimos and Chuckchi (Thomasson et al., 1992, Avksentyuk et al., 1994).
The purpose of the present study was to compare the variation in genes that are involved in alcohol metabolism among the Greenland Inuit with published results from the general population of Denmark and Han Chinese. Specifically, we wanted to test the hypothesis that the Inuit carried the allele of ALDH encoding inactive acetaldehyde dehydrogenase which has been found among East Asians. Secondly, we wanted to analyze if the association between such genes and drinking patterns among the Inuit were similar to those reported in the literature and thus to determine the role of genetics in drinking behaviour in this indigenous population.
Section snippets
Methods
The data were collected as part of two population surveys in Greenland. Only participants categorized at enrolment as indigenous Greenlanders (synonym: Inuit) based on the primary language of the participant and self-identification were included in the analyses. In 1999–2001, data (N = 1299) were collected by interview and clinical examination in six towns and villages on the west coast of Greenland as part of a general population health survey with a participation rate of 67% (Bjerregaard et
Results
The study base consisted of 4162 Inuit with information about at least one of the SNPs. Among these, 531 were born in East or North Greenland and reported having four Inuit grandparents. These were considered the least admixed Inuit. Information about alcohol consumption was available for 3560 participants. Table 1 shows the characteristics of the study populations. Non-drinkers made up 17% among men and 23% among women, heavy drinkers 14% among men and 11% among women; 35% and 22%,
Discussion
The study is the largest study of SNPs related to alcohol metabolism among the Inuit. Alcohol problems have been a major public health problem in this population since the 1950s and both among lay persons and health professionals the role of genetics has been debated. The present study clearly shows that the protective Asian genotype is not present among the Inuit but that the prevalence of other alcohol related SNPs may be important. Drinking patterns were self-reported which may introduce a
Role of funding sources
None of the funding sources had any role in study design, collection, analysis or interpretation of data.
Contributors
PB made data collection and analyzed the data with assistance from SSM. PB and JST had designed the study. UB designed the questionnaire for drinking patterns. TH managed the genetic analyses. Later, PB wrote the first draft of the manuscript. Finally, all authors made a fair amount of contribution and approved the final manuscript.
Conflict of interest
No conflict declared.
Acknowledgements
The study was supported by Karen Elise Jensen's Foundation, NunaFonden, Medical Research Council of Denmark, Medical Research Council of Greenland and the Commission for Scientific Research in Greenland.
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