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CORRESPONDENCE The amount of alcohol consumed correlates with
the values of different laboratory parameters. Although one of the most
frequently used markers of alcohol consumption is the erythrocyte mean
cell volume (MCV), the extent of the increase of MCV varies from one individual to another.1 This cannot be explained only by
inaccuracies in measuring alcohol intake by interviews or
questionnaires. The major enzymes responsible for alcohol metabolism
are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
Among the ADH and ALDH genes, the polymorphisms of ADH2 and
ALDH2 are thought to contribute to individual differences in the
elimination rates of alcohol and acetaldehyde,
respectively.2 In this study, we examined the relations
between the polymorphisms of these genes and the levels of MCV in drinkers. The subjects were 133 male workers aged 25 to 59 years (average, 46 years) who drank more than 300 g alcohol per week (average, 375 g). Informed consent was obtained from all subjects. DNA was extracted from peripheral blood leukocytes. The ADH2
genotype was determined by polymerase chain reaction and
subsequent digestion with MaeIII according to the
method of Xu et al.3 The ALDH2 genotype was
determined based on amplified product length polymorphism analysis
using 3 oligonucleotide primers according to the method described by
Aoshima et al.4 For statistical analysis, the Tukey
multiple comparison test was used to assess significant differences
between group means. Analysis of covariance was used to estimate the
means of variables adjusted for the confounding variables. In the 133 men, the frequencies of
ALDH21/21,
ALDH21/22, and
ALDH22/22 genotypes were 78.9%,
20.3%, and 0.8%, respectively. The frequency of the
ALDH21/21 genotype was higher, and
the frequencies of the ALDH21/22 and
ALDH22/22 genotypes were lower,
compared with those in Japanese subjects, including drinkers and
nondrinkers.5 This is probably because we examined only
heavy drinkers. When the subjects were divided into the
ALDH21/21,
ALDH21/22, and
ALDH22/22 groups, the
ALDH21/22 group had significantly
higher MCVs than the ALDH21/21 group
(Table 1). No difference in
hemoglobin level between the 2 groups was observed. Similar results
were obtained after correction for age, body-mass index, smoking,
alcohol consumption, and ADH genotype. Because the
ALDH22/22 genotype was observed in
only one subject, we could not compare this group with the other 2 groups. In contrast, when the subjects were divided into the
ADH21/21,
ADH21/22, and
ADH22/22 groups, no difference in
the MCVs and hemoglobin concentration was observed among the 3 groups.
Multiple regression analysis revealed that MCV was positively
associated with the ALDH genotype (P = .0001),
the amount of smoking (P = .0208), and age
(P = .0237), but negatively associated with the body-mass
index (P = .0374). There was no association between MCV
and the amount of consumption or the ADH genotype.
The present study indicated that the extent of the increase of MCV in alcohol drinkers depended on the individual ALDH genotype. Although drinkers are well known to show macrocytosis, the cause of their macrocytosis is not clear. Because the ALDH2 genotype is largely responsible for blood levels of acetaldehyde after alcohol consumption, the macrocytosis observed in drinkers might be caused by increased blood levels of acetaldehyde.
Yoshiaki Hashimoto, Toshifumi Nakayama, Azusa Futamura, Miho Omura, and Kazuhiko Nakahara Supported in part by grants from the Health Science Center Foundation, the Smoking Research Foundation, and the Clinical Pathology Research Foundation of Japan References
1.
Conigrave KM, Saunders JB, Whitfield JB.
Diagnostic tests for alcohol consumption.
Alcohol Alcoholism.
1995;30:13-26 2. Bosron WF, Li T-K. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatol. 1986;6:502-510[Medline] [Order article via Infotrieve]. 3. Xu Y, Carr LG, Bosron WF, Li T-K, Edenberg HJ. Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics. 1988;2:209-214[CrossRef][Medline] [Order article via Infotrieve]. 4. Aoshima T, Umetsu K, Yuasa I, Watanabe G, Suzuki T. Simultaneous genotyping of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) loci by amplified product length polymorphism (APLP) analysis. Electrophoresis. 1998;19:659-660[CrossRef][Medline] [Order article via Infotrieve]. 5. Suzuki Y, Muramatsu T, Taniyama M, et al. Mitochondrial aldehyde dehydrogenase in diabetes associated with mitochondrial tRNALeu (UUR) mutation at position 3243. Diabetes Care. 1996;19:1423-1425[Abstract]   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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