Printer Friendly

Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption.

Epidemiologic studies have consistently shown that light or light to moderate drinkers are at a lower risk of coronary heart disease (CHD) [3] (1-6). The mechanisms of this association include beneficial effects on HDL- and LDL-cholesterol, insulin sensitivity, platelet aggregation, blood coagulation, and fibrinolysis (1-7). However, drinking also has negative effects on blood pressure (8), triglycerides (9), and uric acid (10). These effects could attenuate the cardioprotective effect of alcohol. A recent study suggested that the extent of the negative effects of drinking varied on an individual basis (11). Although the mechanism of this variability is not clear, it may be mediated partly by the speed of alcohol metabolism, the types of alcoholic beverages, the regularity of drinking, and nutritional status.

The major enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) (12). ADH, which metabolizes ethanol to acetaldehyde, is a dimeric protein consisting of two active subunts, and six ADH genes have been characterized (13). Among them, the ADH2 and ADH3 loci are polymorphic. The ADH2 locus has three alleles: [ADH2.sup.1], which encodes for the [[beta].sup.1] subunit with low activity; [ADH2.sup.2], which encodes for the [[beta].sup.2] subunit with high activity; and ADH23, which encodes for the [[beta].sup.3] subunit, which is rarely expressed in Japanese (12). The ADH3 locus has two alleles: [ADH3.sup.1], which encodes for the [[gamma].sup.1] subunit; and [ADH3.sup.2], which encodes for the [[gamma].sup.2] subunit. Because the difference in kinetic properties is much smaller between the [[gamma].sup.1] and [[gamma].sup.2] subunits than between the [[beta].sup.1] and [[beta].sup.2] subunits, the ADH2 gene polymorphism could play an important role in individual variations regarding ethanol elimination (12). On the other hand, ALDH, which converts acetaldehyde to acetate, also has multiple forms. Among them, ALDH2, with a low [K.sub.m], is thought to be responsible for most acetaldehyde oxidation (12). The [ALDH2.sup.1] and [ALDH2.sup.2] genes encode the active and the inactive subunit, respectively (14,15); therefore, the [ALDH2.sup.2] gene contributes to the manifestations of increased blood acetaldehyde after alcohol drinking, e.g., facial flushing, palpitations, and nausea (16,17).

In this study, we examined whether the changes in blood pressure, serum lipids, and uric acid associated with alcohol consumption varied in relation to the polymorphisms in ADH2 and ALDH2.

Participants and Methods

PARTICIPANTS

The participants were 241 male employees from the University of Tokyo Hospital and its affiliated hospitals and institutions, who were not taking any medication for hypertension, diabetes, hyperlipidemia, and hyperuricemia. Genetic polymorphisms were examined in 133 men who drank >300 g of alcohol per week. The other 108 men were nondrinkers. Informed consent was obtained from all participants.

METHODS

Information regarding current medication, smoking habits, physical activity, and alcohol consumption was obtained by questionnaire as described previously (11). Alcohol consumption was recorded as the average weekly frequency and the average daily amount. The participants were asked to convert all types of alcohol consumption to number of bottles of the Japanese rice wine, sake, based on their ethanol content (11). Blood samples were collected in the morning after a fast of [greater than or equal to]12 h. Serum triglycerides, cholesterol, HDL-cholesterol, and uric acid were measured by commercially available enzymatic assays. [gamma]-Glutamyl transpeptidase (rGTP) was measured by an optimized method based on the recommendations of the Japan Society of Clinical Chemistry. Hemoglobin [A.sub.1C] ([HbA.sub.1C]) was measured by HPLC. The reference interval for [HbA.sub.1C] was 4.3-5.8%. LDL-cholesterol was estimated by the Friedewald equation (18) in individuals with triglycerides <4.51 mmol/L.

Genetic polymorphisms were examined as follows. DNA was extracted from peripheral blood leukocytes by a commercially available DNA extraction reagent set (Dr.GenTLE; Takara Biomedicals). The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII, according to the method of Xu et al. (19). The ALDH2 genotype was determined based on amplified product length polymorphism analysis using three oligonucleotide primers, according to the method described by Aoshima et al. (20).

STATISTICAL ANALYSIS

Data were analyzed by the Statistical Analysis System (SAS Institute). The Tukey multiple comparison test or the Student t-test was used to assess significant differences between group means. Systolic blood pressure, HDL-cholesterol, triglycerides, rGTP, and [HbA.sub.1C] were compared after being logarithmically transformed to allow the use of parametric tests. The two-tailed Fisher exact test was used to compare group proportions. Multiple logistic regression analysis was used to calculate odds ratios. Differences with a P < 0.05 were considered statistically significant.

Results

We first compared lifestyle habits, blood pressure, and laboratory data between the drinkers and the nondrinkers (Table 1). The drinkers smoked more than the nondrinkers; they also had significantly higher blood pressure, HDL-cholesterol, triglycerides, uric acid, and rGTP and significantly lower LDL-cholesterol and [HbA.sub.1C].

Among the 133 drinkers, the frequencies of the [ADH2.sup.1]/[2.sup.1], [ADH2.sup.1]/[2.sup.2], and [ADH2.sup.2]/[2.sup.2] genotypes were 21.8%, 31.6%, and 46.6%, respectively, whereas those of the [ALDH2.sup.1]/[2.sup.1], [ALDH2.sup.1]/[2.sup.2], and [ALDH2.sup.2]/[2.sup.2] genotypes were 78.9%, 20.3%,and 0.8%,respectively (Table 2). When the participants were divided into three groups, the [ADH2.sup.1]/[2.sup.1], [ADH2.sup.1]/[2.sup.2], and [ADH2.sup.2]/[2.sup.2] groups, according to the ADH2 genotypes, there were no significant differences in age, body mass index, lifestyle habits, or frequency of the ALDH genotypes. The mean triglycerides and rGTP values were significantly higher in the [ADH2.sup.2]/[2.sup.2] group than in the [ADH2.sup.1]/[2.sup.1] group. No differences were observed among the three groups in blood pressure, total cholesterol, LDL--and HDL-cholesterol, uric acid, or [HbA.sub.1C]. When the participants were divided into two groups, the [ALDH2.sup.1]/[2.sup.1] and the ([ALDH2.sup.1]/[2.sup.2] + [ALDH2.sup.2]/[2.sup.2]) groups, no significant differences were observed between the two groups for any of the variables analyzed. Similar results were obtained when the values were adjusted for age, body mass index, smoking, alcohol consumption, and physical activity.

The associations between the ADH2 or ALDH2 genotype and the risk factors for CHD were further assessed by multiple logistic regression analysis (Table 3). The odds ratios for the participants whose values for the difference variables were in the highest one third were calculated after corrections for age, body mass index, smoking, alcohol consumption, physical activity, and ALDH2 or ADH2 genotype. The [ADH2.sup.2]/[2.sup.2] group had significantly higher odds ratios for systolic blood pressure (odds ratio, 3.1), triglycerides (odds ratio, 3.2), and uric acid (odds ratio, 4.1) compared with the [ADH2.sup.1]/[2.sup.1] group. In contrast, no significant differences were observed between the two ALDH2 groups for any of the valuables analyzed.

Discussion

The present study indicates that the ADH2 genotype, but not the ALDH2 genotype, might be involved in individual variations in blood pressure, triglycerides, and uric acid in relation to alcohol consumption. This is the first report showing a relationship between ADH2 genotype and risk factors for CHD. The findings suggest that the most appropriate amount of drinking for cardioprotection differs among individuals with different ADH2 genotypes. The distribution of the ADH2 genotypes is reported to be quite different in Japanese, Chinese, African Americans, and Brazilians (12). This may be one of the reasons for the considerable inconsistency regarding the amount of alcohol consumption that provides cardioprotective effects (5). The ratio of ADH to ALDH is believed to play a more important role in alcohol metabolism in the case of light to moderate alcohol consumption (21). At higher consumption, other pathways may play a more important role. Because the drinkers in the present study were moderate to heavy drinkers, it will be important to examine light to moderate drinkers. Furthermore, it will be interesting to examine the relationship between the ADH2 genotype and other risk factors for CHD, such as insulin resistance, platelet aggregation, fibrinogen, and plasminogen activator inhibitor 1.

It is not clear at present what mediates the association between the ADH2 genotype and such responses to alcohol drinking. Our results support those of reports showing no association between blood pressure and the ALDH2 genotype (22, 23). Because the ALDH2 genotype largely influences blood acetaldehyde concentrations after alcohol consumption (24), the presence of acetaldehyde in the blood is probably not the chief cause of increases in those risk factors associated with drinking. In contrast, the involvement of the ADH2 genotype in individual variations in such responses to drinking suggests an important role of the ADH2 isoenzymes in differences in alcohol metabolism. It is reported that there is a two--to threefold variation in alcohol elimination rate (25-27). A study in mono--and dizygotic twins showed that approximately one-half of this variability is attributable to genetic factors (28). The only ADH genes exhibiting polymorphisms are ADH2 and ADH3, and the kinetic properties show only a small difference among ADH3 isoenzymes (12). Therefore, it is reasonable to assume that the ADH2 genotype accounts for the differences in alcohol elimination rates. Although drinkers with the [ADH2.sup.2]/[2.sup.2] genotype who had a high alcohol elimination rate had higher triglycerides and rGTP concentrations, this can not be attributed to acetaldehyde accumulated in the blood, as described above; it may be caused by metabolic changes accompanying the oxidation of alcohol to acetaldehyde by ADH, such as an increase in the NADH:NAD ratio (29), increases in the concentrations of reactive oxygen species (30, 31), and other factors, although there is no evidence against this hypothesis.

Our study participants who were moderate to heavy drinkers showed significantly higher frequencies of the [ADH2.sup.1]/[2.sup.1] and [ALDH2.sup.1]/[2.sup.1] genotypes and lower frequencies of the [ALDH2.sup.1]/[2.sup.2] and [ALDH2.sup.2]/[2.sup.2] genotypes compared with Japanese, including drinkers and nondrinkers, who participated in other studies (17, 32, 33). This is probably because our study groups included only drinkers. This idea is supported by studies involving individuals with alcoholism or alcoholic liver diseases, who showed frequencies of the ADH2 and ALDH2 genotypes similar to those observed in the present study (34-36). A high prevalence of the [ADH2.sup.1]/[2.sup.1] genotype in drinkers also suggests that the ADH genotype plays an important role in alcohol metabolism after heavy drinking, although one published study showed that the ADH genotype does not influence the alcohol elimination rate after moderate drinking (24).

In conclusion, we showed that the ADH2 genotype influences the responses of blood pressure, triglycerides, and uric acid to alcohol consumption. We do not believe that this influence was mediated by the acetaldehyde concentration in the blood because the ALDH2 genotype did not influence those variables. The present findings suggest that the amount of alcohol intake that provides cardioprotective effects varies on an individual basis. Further studies in a larger population, including drinkers and nondrinkers, will be needed to confirm that the findings obtained from the present study are correct and that the ADH genotype does not influence the risk factors for CHD in nondrinkers.

This study was supported in part by grants from the Health Science Center Foundation, the Smoking Research Foundation, and the Clinical Pathology Research Foundation of Japan.

Received January 21, 2002; accepted April 24, 2002.

References

(1.) Savolainen MJ, Kesaniemi YA. Effects of alcohol on lipoproteins in relation to coronary heart disease. Curr Opin Lipidol 1995;6:243-50.

(2.) Klatsky AL, Friedman GD. Annotation: alcohol and longevity. Am J Public Health 1995;85:16-8.

(3.) Bell DSH. Alcohol and the NIDDM patient. Diabetes Care 1996; 19:509-13.

(4.) Chick J. Alcohol, health, and the heart: implications for clinicians. Alcohol Alcohol 1998;33:576-91.

(5.) Wannamethee SG, Shaper AG. Alcohol, coronary heart disease and stroke: an examination of the J-shaped curve. Neuroepidemiology 1998;17:288-95.

(6.) Gall N. Is wine good for your heart? A critical review. Postgrad Med J 2001;77:172-6.

(7.) Mukamal KJ, Jadhav PP, D'Agostino RB, Massaro JM, Mittleman MA, Lipinska I, et al. Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort. Circulation 2001; 104:1367-73.

(8.) Cushman WC. Alcohol consumption and hypertension. J Clin Hypertens 2001;3:166-70.

(9.) Nagaya T, Yoshida H, Takahashi H, Matsuda Y, Kawai M. Dose-response relationships between drinking and serum tests in Japanese men aged 40-59 years. Alcohol 1999;17:133-8.

(10.) Nakanishi N, Yoshida H, Nakamura K, Suzuki K, Tatara K. Predictors for development of hyperuricemia: an 8-year longitudinal study in middle-aged Japanese men. Metabolism 2001;50: 621-6.

(11.) Hashimoto Y, Futamura A, Nakarai H, Nakahara K. Relationship between response of y-glutamyl transpeptidase to alcohol drinking and risk factors for coronary heart disease. Atherosclerosis 2001;158:465-70.

(12.) Bosron WF, Li T-K. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 1986;6:502-10.

(13.) Pastino GM, Flynn EJ, Sultatos LG. Genetic polymorphisms in ethanol metabolism: issues and goals for physiologically based pharmacokinetic modeling. Drug Chem Toxicol 2000;23:179-201.

(14.) Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A. Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2. Proc Natl Acad Sci U S A 1985;82:3771-5.

(15.) Yoshida A, Ikawa M, Hsu LC, Tani K. Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases. Alcohol 1985; 2:103-6.

(16.) Harada S, Aganval DP, Goedde HW. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet 1981;2:982.

(17.) Takeshita T, Morimoto K, Mao XQ, Hashimoto T, Furuyama J. Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population. Hum Genet 1994;94: 217-23.

(18.) Friedewald WE, Levy RI, Frederickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.

(19.) 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;2:209-14.

(20.) 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;19:659-60.

(21.) Lands WEM. A review of alcohol clearance in humans. Alcohol 1998;15:147-60.

(22.) Tsuritani I, Ikai E, Date T, Suzuki Y, Ishizaki M, Yamada Y. Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship. Am J Hypertens 1995;8: 1053-9.

(23.) Okayama A, Ueshima H, Yamakawa M, Kita Y. Low-Km aldehyde dehydrogenase deficiency does not influence the elevation of blood pressure by alcohol. J Hum Hypertens 1994;8:205-8.

(24.) Mizoi Y, Yamamoto K, Ueno Y, Fukunaga T, Harada S. Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism. Alcohol Alcohol 1994; 29:707-10.

(25.) Bennion U, Li T-K. Alcohol metabolism in American Indians and whites: lack of racial differences in metabolic rate and liver alcohol dehydrogenase. N Engl J Med 1976;294:9-13.

(26.) Kopun M, Propping P. The kinetics of ethanol absorption and elimination in twins and supplementary repetitive experiments in singleton subjects. Eur J Clin Pharmacol 1977;11:337-44.

(27.) Keiding S, Christensen NJ, Damgaard SE, Dejgard A, Iversen HL, Jacobsen A, et al. Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake. Biochem Pharmacol 1983; 32:3097-102.

(28.) Martin NG, Perl J, Oakeshott JG, Gibson JB, Starmer GA, Wilks AV. A twin study of ethanol metabolism. Behavior Genetics 1985;15: 93-109.

(29.) Baraona E, Lieber CS. Effects of ethanol on lipid metabolism. J Lipid Res 1979;20:289-315.

(30.) Kurose I, Higuchi H, Kato S, Miura S, Watanabe N, Kamegaya Y, et al. Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol. Gastroenterology 1997;112:1331-43.

(31.) Bailey SM, Cunningham CC. Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes. Hepatology 1998;28:1318-26.

(32.) Takeshita T, Mao X, Morimoto K. The contribution of polymorphism in the alcohol dehydrogenase R subunit to alcohol sensitivity in a Japanese population. Hum Genet 1996;97:409-13.

(33.) Suzuki Y, Muramatsu T, Taniyama M, Atsumi Y, Suematsu M, Kawaguchi R, et al. Mitochondrial aldehyde dehydrogenase in diabetes associated with mitochondrial [tRNA.sup.Leu] (UUR) mutation at position 3243. Diabetes Care 1996;19:1423-5.

(34.) Yamauchi M, Maezawa Y, Mizuhara Y, Ohata M, Hirakawa J, Nakajima H, et al. Polymorphisms in alcohol metabolizing enzyme genes and alcohol cirrhosis in Japanese patients: a multivariate analysis. Hepatology 1995;22:1136-42.

(35.) Tanaka F, Shiratori Y, Yokosuka 0, Imazeki F, Tsukada Y, Omata M. High incidence of ADH2*1/ALDH2*1 genes among Japanese alcohol dependents and patients with alcoholic liver disease. Hepatology 1996;23:234-9.

(36.) Thomasson HR, Crabb DW, Edenberg HJ, Li T-K. Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behav Genet 1993;23:131-6.

[3] Nonstandard abbreviations: CHD, coronary heart disease; ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; rGTP, [gamma]-glutamyl transpeptidase; and Hb, hemoglobin.

YOSHIAKI HASHIMOTO, [1] * TOSHIFUMI NAKAYAMA, [2] AZUSA FUTAMURA, [1] MIHO OMURA, [1] HIDEO NAKARAI, [1] and KAZUHIKO NAKAHARA [1]

Departments of [1] Clinical Laboratory Medicine and [2] Internal Medicine, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

* Author for correspondence. Fax 81-3-5689-0495; e-mail d01009@h.u-tokyo.ac.jp.
Table 1. Clinical characteristics of drinkers and
nondrinkers. (a)

 Drinkers Nondrinkers

n 133 108
Age, years 46.0 (0.6) (b) 48.0 (0.7)
Body mass index, kg/[m.sup.2] 22.5 (0.2) 22.7 (0.2)
Exercise, times/month 2.6 (0.3) 2.0 (0.3)
Alcohol, g/week 17.1 (0.4) (c) 0 (0)
Smoking, cigarettes/day 13.9 (1.3) (c) 6.1(1.0)
Not adjusted
Systolic BP, (d) mmHg 126.9 (1.2) (c) 118.9 (1.4)
Diastolic BP, mmHg 81.5 (0.9) (c) 76.6 (0.9)
Total cholesterol, mmol/L 5.32 (0.08) 5.31 (0.07)
LDL-cholesterol, (e) mmol/L 2.87 (0.06) (c) 3.30 (0.06)
HDL-cholesterol, mmol/L 1.68 (0.04) (c) 1.42 (0.03)
Triglycerides, mmol/L 1.68 (0.12) (c) 1.28 (0.06)
Uric acid, [micro]m?l/L 349 (5) (b) 327 (6)
rGTP, U/L 48.9 (4.1) (c) 21.9 (1.7)
[HbA.sub.1c], % 5.12 (0.03) (b) 5.24 (0.04)
Adjusted for age, body mass
 index, and smoking
Systolic BP, mmHg 127.2 (1.2) (c) 118.5 (1.4)
Diastolic BP, mmHg 82.4 (0.8) (c) 75.5 (0.9)
Total cholesterol, mmol/L 5.35 (0.07) 5.27 (0.08)
LDL-cholesterol, (e) mmol/L 2.90 (0.06) (c) 3.27 (0.07)
HDL-cholesterol, mmol/L 1.70 (0.03) (c) 1.40 (0.04)
Triglycerides, mmol/L 1.67 (0.10) (b) 1.30 (0.11)
Uric acid, [micro]m?l/L 350 (6) (c) 325 (7)
rGTP, U/L 50.1 (3.3) (c) 20.3 (3.7)
[HbA.sub.1c], % 5.12 (0.04) (b) 5.24 (0.04)

(a) Values are the mean (SE).

(b,c) Compared with nondrinkers: P <0.05; P <0.01.

(d) BP, blood pressure.

(e) Results in participants with triglycerides <4.51 mmol/L
(130 drinkers, 108 nondrinkers).

Table 2. Clinical characteristics of the participants
distributed according to their ADH2 and ALDH2 genotypes. (a)

 ADH2 genotype

 [2.sup.1]/ [2.sup.1]/
 [2.sup.1] [2.sup.2]

n 29 42
Age, years 46.3 (1.4) 46.2 (1.0)
Body mass index, kg/[m.sup.2] 22.1 (0.4) 22.3 (0.2)
Exercise, times/month 2.9 (0.5) 2.0 (0.4)
Alcohol, g/week 376 (14) 361 (13)
Smoking, cigarettes/day 15.2 (3.0) 11.6 (2.1)
ALDH [2.sup.1]/[2.sup.1]: 82.8: 13.8: 3.4 78.6: 21.4: 0
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
ADH [2.sup.1]/[2.sup.1]:
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
Not adjusted
Systolic BP, (b) mmHg 123.4 (2.7) 125.5 (1.7)
Diastolic BP, mmHg 78.2 (2.2) 82.5 (1.3)
Total cholesterol, mmol/L 5.33 (0.13) 5.22 (0.13)
LDL-cholesterol, (c) mmol/L 2.92 (0.14) 2.84 (0.10)
HDL-cholesterol, mmol/L 1.84 (0.10) 1.67 (0.06)
Triglycerides, mmol/L 1.24 (0.14) 1.51 (0.14)
Uric acid, [micro]mol/L 333 (11) 345 (9)
rGTP, U/L 34.8 (4.9) 51.5 (8.1)
[HbA.sub.1c], % 5.08 (0.05) 5.07 (0.05)
Adjusted for age, body mass
 index, smoking, alcohol
 consumption, exercise,
 and ADH or ALDH genotype
Systolic BP, mmHg 123.7 (2.4) 126.2 (2.0)
Diastolic BP, mmHg 78.6 (1.8) 82.5 (1.5)
Total cholesterol, mmol/L 5.35 (0.16) 5.18 (0.14)
LDL-cholesterol, (c) mmol/L 2.94 (0.13) 2.83 (0.11)
HDL-cholesterol, mmol/L 1.83 (0.08) 1.64 (0.07)
Triglycerides, mmol/L 1.27 (0.25) 1.52 (0.21)
Uric acid, [micro]mol/L 334 (12) 346 (10)
rGTP, U/L 35.5 (8.8) 51.1 (7.4)
[HbA.sub.1c], % 5.08 (0.07) 5.07 (0.06)

 ADH2 genotype ALDH2 genotype

 [2.sup.2]/ [2.sup.1]/
 [2.sup.2] [2.sup.1]

n 62 105
Age, years 45.8 (0.8) 46.0 (0.7)
Body mass index, kg/[m.sup.2] 22.7 (0.2) 22.5 (0.2)
Exercise, times/month 2.9 (0.4) 2.6 (0.3)
Alcohol, g/week 390 (13) 384 (9)
Smoking, cigarettes/day 14.8 (2.1) 14.2 (1.6)
ALDH [2.sup.1]/[2.sup.1]: 77.4: 22.6: 0
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
ADH [2.sup.1]/[2.sup.1]: 22.9: 31.4: 45.7
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
Not adjusted
Systolic BP, (b) mmHg 129.5 (1.8) 127.2 (1.4)
Diastolic BP, mmHg 82.4 (1.2) 81.7 (1.0)
Total cholesterol, mmol/L 5.39 (0.12) 5.30 (0.08)
LDL-cholesterol, (c) mmol/L 2.88 (0.09) 2.88 (0.07)
HDL-cholesterol, mmol/L 1.62 (0.06) 1.69 (0.04)
Triglycerides, mmol/L 2.00 (0.22) (d) 1.56 (0.08)
Uric acid, [micro]mol/L 357 (9) 345 (6)
rGTP, U/L 53.7 (6.3) (e) 46.9 (4.1)
[HbA.sub.1c], % 5.16 (0.05) 5.14 (0.03)
Adjusted for age, body mass
 index, smoking, alcohol
 consumption, exercise,
 and ADH or ALDH genotype
Systolic BP, mmHg 128.9 (1.7) 127.1 (1.3)
Diastolic BP, mmHg 82.2 (1.2) 81.7 (0.9)
Total cholesterol, mmol/L 5.40 (0.11) 5.30 (0.09)
LDL-cholesterol, (c) mmol/L 2.88 (0.09) 2.88 (0.07)
HDL-cholesterol, mmol/L 1.64 (0.06) 1.69 (0.04)
Triglycerides, mmol/L 1.97 (0.17) (d) 1.57 (0.13)
Uric acid, [micro]mol/L 357 (8) 346 (6)
rGTP, U/L 53.6 (6.0) (e) 46.9 (4.6)
[HbA.sub.1c], % 5.16 (0.04) 5.14 (0.03)

 ALDH2 genotype

 [2.sup.1]/[2.sup.2] +
 [2.sup.2]/[2.sup.2]

n 28
Age, years 46.2 (1.1)
Body mass index, kg/[m.sup.2] 22.2 (0.3)
Exercise, times/month 2.6 (0.5)
Alcohol, g/week 357 (13)
Smoking, cigarettes/day 12.7 (2.6)
ALDH [2.sup.1]/[2.sup.1]:
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
ADH [2.sup.1]/[2.sup.1]: 17.9: 32.1: 50.0
 [2.sup.1]/[2.sup.2]:
 [2.sup.2]/[2.sup.2]
Not adjusted
Systolic BP, (b) mmHg 125.8 (2.2)
Diastolic BP, mmHg 80.7 (1.8)
Total cholesterol, mmol/L 5.41 (0.20)
LDL-cholesterol, (c) mmol/L 2.84 (0.13)
HDL-cholesterol, mmol/L 1.65 (0.09)
Triglycerides, mmol/L 2.11 (0.47)
Uric acid, [micro]mol/L 363 (13)
rGTP, U/L 56.2 (11.9)
[HbA.sub.1c], % 5.02 (0.05)
Adjusted for age, body mass
 index, smoking, alcohol
 consumption, exercise,
 and ADH or ALDH genotype
Systolic BP, mmHg 127.0 (2.5)
Diastolic BP, mmHg 81.2 (1.9)
Total cholesterol, mmol/L 5.37 (0.17)
LDL-cholesterol, (c) mmol/L 2.79 (0.14)
HDL-cholesterol, mmol/L 2.12 (0.26)
Triglycerides, mmol/L 2.12 (0.26)
Uric acid, [micro]mol/L 363 (12)
rGTP, U/L 57.9 (9.1)
[HbA.sub.1c], % 5.01 (0.07)

(a) Values are the mean (SE).

(b) BP, blood pressure.

(c) Results in the participants with triglycerides <4.51 mmol/L.

(d, e) Compared with ADH [2.sup.1]/[2.sup.1]:

(d) P <0.01; (e) P <0.05.

Table 3. Prevalences and odds ratios for the participants
for whom values for the variables listed were in the
highest one third.

 ADH genotype

 [2.sup.1]/ [2.sup.1]/
 [2.sup.1] [2.sup.2]

Systolic BP (a) [greater 17.2 33.3
 than or equal
 to]132 mmHg, %
OR (b) (95% CI) 1 2.8 (0.8-9.3)
Diastolic BP [greater 24.1 33.3
 than or equal
 to]85 mmHg, %
OR (95% CI) 1 1.6 (0.5-4.8)
Total cholesterol 20.7 31.0
 [greater than
 or equal to]5.59
 mmol/L, %
OR (95% CI) 1 1.6 (0.5-5.1)
LDL-cholesterol [greater 37.9 26.8
 than or equal
 to]3.15 mmol/L, %
OR (95% CI) 1 0.5 (0.2-1.5)
HDL-cholesterol 44.8 28.6
 [greater than
 or equal to]1.84
 mmol/L, %
OR (95% CI) 1 0.4 (0.1-1.1)
Triglycerides [greater 17.2 31.0
 than or equal
 to]1.85 mmol/L, %
OR (95% CI) 1 2.1 (0.6-6.8)
Uric acid [greater 17.2 33.3
 than or equal
 to]375 mmol/L, %
OR (95% CI) 1 2.5 (0.7-8.6)
[HbA.sub.1c] [greater 34.6 37.5
 than or equal
 to]5.2%, %
OR (95% CI) 1 1.1 (0.4-3.1)
rGTP [greater than 17.2 35.7
 or equal to]53
 U/L, %
OR (95% CI) 1 2.5 (0.8-8.2)

 ALDH genotype

 [2.sup.2]/ [2.sup.1]/
 [2.sup.2] [2.sup.1]

Systolic BP (a) [greater 41.9 (c) 34.3
 than or equal
 to]132 mmHg, %
OR (b) (95% CI) 3.1 (1.0-9.7) (c) 1
Diastolic BP [greater 40.3 33.3
 than or equal
 to]85 mmHg, %
OR (95% CI) 2.0 (0.7-5.7) 1
Total cholesterol 40.3 31.4
 [greater than
 or equal to]5.59
 mmol/L, %
OR (95% CI) 2.8 (0.9-8.0) 1
LDL-cholesterol [greater 36.7 34.6
 than or equal
 to]3.15 mmol/L, %
OR (95% CI) 0.9 (0.4-2.4) 1
HDL-cholesterol 30.7 34.3
 [greater than
 or equal to]1.84
 mmol/L, %
OR (95% CI) 0.5 (0.2-1.4) 1
Triglycerides [greater 41.9 (c) 32.4
 than or equal
 to]1.85 mmol/L, %
OR (95% CI) 3.2 (1.1-9.8) (c) 1
Uric acid [greater 45.2 (c) 35.2
 than or equal
 to]375 mmol/L, %
OR (95% CI) 4.1 (1.3-13.1) (c) 1
[HbA.sub.1c] [greater 37.7 39.0
 than or equal
 to]5.2%, %
OR (95% CI) 1.1 (0.4-3.1) 1.0
rGTP [greater than 37.1 30.5
 or equal to]53
 U/L, %
OR (95% CI) 2.8 (0.9-8.5) 1

 ALDH genotype

 [2.sup.1]/[2.sup.2]
 [2.sup.2]/[2.sup.2]

Systolic BP (a) [greater 32.1
 than or equal
 to]132 mmHg, %
OR (b) (95% CI) 1.1 (0.4-2.9)
Diastolic BP [greater 39.3
 than or equal
 to]85 mmHg, %
OR (95% CI) 1.5 (0.6-3.6)
Total cholesterol 39.3
 [greater than
 or equal to]5.59
 mmol/L, %
OR (95% CI) 1.3 (0.5-3.1)
LDL-cholesterol [greater 30.8
 than or equal
 to]3.15 mmol/L, %
OR (95% CI) 0.7 (0.3-1.9)
HDL-cholesterol 28.6
 [greater than
 or equal to]1.84
 mmol/L, %
OR (95% CI) 0.8 (0.3-2.0)
Triglycerides [greater 35.7
 than or equal
 to]1.85 mmol/L, %
OR (95% CI) 1.2 (0.5-3.1)
Uric acid [greater 35.7
 than or equal
 to]375 mmol/L, %
OR (95% CI) 1.1 (0.4-2.8)
[HbA.sub.1c] [greater 29.6
 than or equal
 to]5.2%, %
OR (95% CI) 0.6 (0.3-1.7)
rGTP [greater than 39.3
 or equal to]53
 U/L, %
OR (95% CI) 1.5 (0.6-3.7)

(a) BP, blood pressure; OR, odds ratio;
CI, confidence interval.

(b) Odds ratio for systolic blood pressure was
corrected for age, body mass index, smoking,
alcohol consumption, physical activity, and
ADH or ALDH genotype.

(c) P <0.05 vs ADH[2.sup.1]/[2.sup.1].
COPYRIGHT 2002 American Association for Clinical Chemistry, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Lipids, Lipoproteins, and Cardiovascular Risk Factors
Author:Hashimoto, Yoshiaki; Nakayama, Toshifumi; Futamura, Azusa; Omura, Miho; Nakarai, Hideo; Nakahara, Ka
Publication:Clinical Chemistry
Date:Jul 1, 2002
Words:4970
Previous Article:Quantification of pro-B-type natriuretic peptide and its products in human plasma by use of an analysis independent of precursor processing.
Next Article:Determination of sulpiride by capillary electrophoresis with end-column electrogenerated chemiluminescence detection.
Topics:


Related Articles
The ubiquitous, lipids and related diseases: A laboratory perspective.
Treatment of patients with lipid disorders in the primary care setting: new treatment guidelines and their implications. (Review Article).
Alcohol consumption: an overview of benefits and risks.
Bariatric surgery lowers cardiovascular risk: study monitored eight markers of cardiovascular risk, all of which were improved by gastric bypass.
Absence of ABCA1 mutations in individuals with low serum HDL-cholesterol.
Synergistic effect between apolipoprotein E and angiotensinogen gene polymorphisms in the risk for early myocardial infarction.
Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men:...
Apolipoprotein E in apolipoprotein B (apo B)- and non-apo B-containing lipoproteins in 3523 participants in the Stanislas cohort: Biological...
The MTHFR C677T, APOE, and PON55 gene polymorphisms show relevant interactions with cardiovascular risk factors.
High lipoprotein-associated phospholipase [A.sub.2] is a risk factor for recurrent coronary events in postinfarction patients.

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters