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RESEARCH REPORT |
1 Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan; and
2 Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine;
* corresponding author, shizuku{at}dent.osaka-u.ac.jp
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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3.5 mm was used as a periodontal parameter. ALDH2 genotypes were determined with the use of a PCR/RFLP method. Multiple logistic analyses showed that alcohol consumption was significantly associated with periodontitis, and its odds ratio was 1.98. There was no significant relationship between periodontal status and ALDH2 genotypes. However, ALDH2*1/*2 subjects who consumed 33 g/day of alcohol had a significantly greater percentage of pocket depths 3.5 mm than those whose daily consumption was lower, while there was no significant difference in periodontal status associated with alcohol consumption in ALDH2*1/*1 subjects. Our results suggest that alcohol consumption may be a risk indicator for periodontitis in ALDH2*1/*2 subjects who consume larger amounts of alcohol.
KEY WORDS: alcohol consumption • periodontitis • ALDH2 genotype • epidemiology
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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SUBJECTS & METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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Assessment of Lifestyle
Lifestyle behavior was covered by 103 items in a self-administered questionnaire and included cigarette smoking, alcohol consumption, sleeping hours, breakfast consumption, nutritional balance, working hours, physical exercise, and mental health (Kusaka et al., 1992). The questions were multiple choice, with 2 to 6 possible answers for each. We also asked questions regarding 34 items of oral health behavior (e.g., frequency of toothbrushing, method of brushing cervical teeth, use of an inter-dental brush) by a self-administered questionnaire. Each answer was dichotomized as a "good" or "not good" health practice. We calculated pack-years to evaluate cigarette smoking status, and levels of smoking were separated into high ( 15.0) pack-years and low (< 15.0) pack-years, which were above and below, respectively, the higher 20th percentile of the distribution. In addition, we calculated body mass index (BMI) to evaluate physical factors, and the subjects were classified into 2 groups, BMI < 25 and BMI 25.
Assessment of Alcohol Consumption
Information on drinking frequency, mean amounts of alcohol consumption per occasion, and kinds of alcoholic beverages—including beer, sake, wine, whisky, shochu (a distilled alcoholic beverage made from wheat or sweet potatoes), and others—was obtained by a self-administered questionnaire. We calculated average daily alcohol consumption by multiplying the mean amount of alcohol consumption per occasion by drinking frequency. Alcohol content was estimated to be 20.0 g for a bottle of beer, 22.0 g for a cup of sake, 20.0 g for a glass of whisky, 50.0 g for a cup of shochu, and 12.0 g for a glass of wine (Japan Health Promotion and Fitness Foundation, 2001).
Determination of ALDH2 and ADH2 Genotypes
Blood samples (2–4 mL) were obtained with permission from 235 of the subjects. DNA was extracted from 100 µL of white-blood-cell-rich plasma by means of an Isoquick kit (MicroProbe, Garden Grove, CA, USA). The polymorphism on exon 12 of the ALDH2 gene was determined with the use of a polymerase-chain-reaction/restriction-fragment-length polymorphism (PCR-RFLP) method (Takeshita et al. 1994). Briefly, the exon was amplified by 30–35 cycles of PCR (1 min at 94°C, 1 min at 50°C, and 30 sec at 72°C). One amplification primer contained a base substitution to create Ksp632I (Boehringer Mannheim, Mannheim, Germany) at 37°C for 3–6 hrs. Digested samples were separated on gels containing 3% NuSieve GTG agarose (FMC Bioproducts, Rockland, ME, USA) and 1% regular agarose (Sigma, St. Louis, MO, USA), and were stained with ethidium bromide. The ADH2 genotypes were determined according to a method described previously (Xu et al., 1988), with PCR and MaeIII digestion.
Assessment of Periodontitis
Two examiners conducted the clinical examinations, which included probing pocket depth (PPD) measurements, using an automated probe (Vivadent, Schaan, Liechtenstein) with a constant force of 20 g applied to all teeth present, except for third molars. Each subject was examined for PPD at 6 sites per tooth, and the deepest was recorded for each. The percentage of teeth with a PPD greater than 3.5 mm was assessed as a periodontal parameter. Subjects were then classified into 2 groups, based on being above or below the upper 20th percentile of the percentage, as periodontitis or non-periodontitis, respectively. Calibrated examiners performed the periodontal examinations. The kappa value for PPD between the two examiners was 0.76, when a PPD of 3.5 mm was used as the cut-off point. The examiners were blind to subjects’ alcohol consumption status.
Statistical Analysis
Data were analyzed by means of the SPSS statistical package (SPSS Inc., Chicago, IL, USA). The associations between periodontitis and surveyed lifestyle variables, including alcohol consumption, along with ADH2 and ALDH2 genotypes, were examined by a Mann-Whitney U test or a Kruskal-Wallis test. We used logistic regression analyses to determine which variables demonstrated a significant independent effect on periodontitis. Odds ratios and their 95% confidence intervals (CI) were also calculated. In addition, linear trends for risk were evaluated based on the mean values for each category of alcohol consumption. All reported P values are two-tailed, and those less than 0.05 were considered statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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3.5 mm varied from 0.0% to 100.0%, with a mean (± SD) of 33.0% (± 27.8%) and the upper 20th percentile of 60.0%. By bivariate analysis, the significant variables related to periodontitis were age, gender, BMI, smoking habit, alcohol consumption, and frequency of toothbrushing (P < 0.05, Table 1
). The independent effects of the variables showing bivariate associations with periodontal disease were tested by multiple logistic regression analysis (Table 2). The significant variables in the model were age, BMI, smoking, and alcohol consumption, P < 0.05), with alcohol consumption showing an odds ratio of 1.98 (95% CI: 1.04–3.76).
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33.0 g/day of alcohol (P for trend = 0.0022), as compared with 0.0 g/day of alcohol. Although there was a significant trend (P for trend = 0.0251), the highest category of alcohol consumption did not show a significant odds ratio (2.04, 95% CI: 0.92–4.57) after an additional adjustment for smoking (data not shown).
The frequencies of ADH2*1/*1, -*1/*2, and -*2/*2 were 6%, 33%, and 60%, respectively, and those of ALDH2*1/*1, -*1/*2, and -*2/*2 were 55%, 39%, and 6%, respectively (Table 3). Although there was no significant difference in alcohol consumption among ADH2 genotypes, the subjects with ALDH2*1/*1 drank significantly more than those with ALDH2*1/*2 and ALDH2*2/*2. No significant difference in periodontal status was found between the ADH2 and ALDH2 polymorphism subjects (Table 3).
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). ALDH2*1/*2 and *1/*1 subjects were classified into those who drank less than 33 g of alcohol per day and those who consumed more. Among the ALDH2*1/*1 genotype group (Table 4), periodontal status did not differ in alcohol consumption level, whereas among the ALDH2*1/*2 genotype group (Table 4), those who drank 33 g or more of alcohol per day showed a significantly higher percentage of PPD 3.5 mm than those who consumed less. In addition, the results of multiple logistic regression analysis were quite different between ALDH2*1/*1 and -*1/*2 genotypes. In ALDH2*1/*1 subjects, there were significant odds ratios for BMI and smoking, but not with alcohol consumption. On the other hand, ALDH2*1/*2 subjects showed significant odds ratios for alcohol consumption and age, even though smoking and other factors were adjusted for.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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3.5 mm after adjustment for age, gender, BMI, smoking habit, and frequency of toothbrushing. We previously found that 60 g or more per day of alcohol intake was an independent risk indicator for periodontitis, according to modified CPI scores (Shizukuishi et al., 1998). A Finnish study also reported that alcohol consumption had an independent association with periodontal health, based on the occurrence of PPD 3.0 mm (Sakki et al., 1995), while the Erie County Study found a positive relationship among alcohol consumption, greater attachment loss, and gingival bleeding (Tezal et al., 2001). This association was also found in a large prospective study (Pitiphat et al., 2003). However, those previous reports did not elucidate the biological effect of alcohol on the risk for periodontitis, and the present is the first known study of both alcohol consumption and alcohol-metabolizing enzyme genotypes.
Researchers have reported that a J-shaped relationship with alcohol consumption was observed regarding cardiovascular disease (Coate, 1993) and bone mineral density (Holbrook and Barrett-Conner, 1993). Tezal et al.(2001) also suggested that the relationship between alcohol consumption and clinical attachment loss might show a J-shape. When we divided the subjects into 4 categories by alcohol consumption, the odds ratio for periodontitis risk among light drinkers (< 33 g/day of alcohol) was reduced, whereas that for heavy drinkers ( 33 g/day of alcohol) was increased, compared with that for non-drinkers. This effect can be plotted as a J-shape. However, when the data were adjusted by age and smoking, there was no significant odds ratio for heavy drinkers. Since our small sample size may have limited our power to detect this association, it is necessary to conduct future studies with a larger population.
Some reports have noted that ALDH2 genotypes are a risk factor for systemic diseases such as liver damage (Shibuya and Yoshida, 1988), alcohol-related asthma (Takada et al., 1994), and cancer (Takeshita et al., 2000). Although alcohol may also have direct effects on systemic diseases, acetaldehyde is generally more harmful to tissues and cells, since the substance is volatile and reacts easily with cellular components such as proteins and DNA, and induces cytotoxicity (Wickramasinghe et al., 1986) and DNA damage (Fang and Vaca, 1995). Thus, such biochemical reactions may cause an adverse effect on host defense. In the present study, there was no significant association seen between periodontal status and ADH2 genotype. Although subjects with ALDH2*1/*2 drank lesser amounts of alcohol daily, as compared with those with ALDH2*1/*1, the former tended to show a higher periodontitis risk. Furthermore, those with ALDH2*1/*2 who drank 33 g/day of alcohol showed a significant periodontitis risk, whereas heavy drinkers with ALDH2*1/*1 did not. The activity in metabolizing acetaldehyde is higher in ALDH2*1/*1 subjects than in ALDH2*1/*2 subjects (Enomoto et al., 1991). If subjects of both genotypes were to drink equally moderate amounts of alcohol, those with ALDH2*1/*2 may have a higher circulating concentration of acetaldehyde than those with ALDH2*1/*1 during consumption. Thus, it seems likely that acetaldehyde more strongly modifies periodontal health in subjects with the ALDH2*1/*2 genotype than in subjects with ALDH2*1/*1.
Since smoking is also an important risk factor for periodontitis and may be correlated with alcohol consumption, some degree of the observed association may be due to a residual complication from smoking. As for a dose-response relationship, we could not evaluate the effect of heavy drinking on the risk of periodontitis after the adjustment for smoking. However, in a multiple logistic regression analysis, there was a significant association between periodontitis and alcohol consumption in all subjects after adjustment for smoking and other factors, and the odds ratio was 1.98 (95% CI: 1.04–3.76). In particular, ALDH2*1/*2 subjects showed alcohol consumption, but not smoking, as a significantly independent variable for periodontal risk in a logistic model. Collectively, alcohol consumption may be a weak risk indicator for periodontitis, but heavy drinkers with ALDH2*1/*2 may have a greater risk. However, longitudinal studies on randomized sample populations will be necessary to clarify the causality between alcohol consumption and periodontitis.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Received March 8, 2003; Last revision November 7, 2003; Accepted November 10, 2003
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS & METHODSRESULTSDISCUSSIONREFERENCES |
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Enomoto N, Takase S, Yasuhara M, Takada A (1991). Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res 15:141–144.[ISI][Medline]
Fang JL, Vaca CE (1995). Development of a 32P-postlabelling method for the analysis of adducts arising through the reaction of acetaldehyde with 2'-deoxyguanosine-3'-monophosphate and DNA. Carcinogenesis 16:2177–2185.
Holbrook TL, Barrett-Connor E (1993). A prospective study of alcohol consumption and bone mineral density. BMJ 306:1506–1509.
Japan Health Promotion and Fitness Foundation (2001). Alcohol. In: Report on promotion of people’s health promotion campaign for the 21st century (Healthy Japan 21). Tokyo: The Foundation, pp. 121–125 (in Japanese).
Kusaka Y, Kondou H, Morimoto K (1992). Healthy lifestyles are associated with higher natural killer cell activity. Prev Med 21:602–615.[ISI][Medline]
Pitiphat W, Merchant AT, Rimm EB, Joshipura KJ (2003). Alcohol consumption increases periodontitis risk. J Dent Res 82:509–513.
Sakki TK, Knuuttila ML, Vimpari SS, Hartikainen MS (1995). Association of lifestyle with periodontal health. Community Dent Oral Epidemiol 23:155–158.[ISI][Medline]
Shibuya A, Yoshida A (1988). Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene [ALDH1(2)] with the disease. Am J Hum Genet 43:744–748.[ISI][Medline]
Shizukuishi S, Hayashi N, Tamagawa H, Hanioka T, Maruyama S, Takeshita T, et al. (1998). Lifestyle and periodontal health status of Japanese factory workers. Ann Periodontol 3:303–311.[Medline]
Takada A, Tsutsumi M, Kobayashi Y (1994). Genotypes of ALDH2 related to liver and pulmonary diseases and other genetic factors related to alcoholic liver disease. Alcohol Alcohol 29:719–727.
Takeshita T, Morimoto K (1996). Effects of genetic polymorphisms in alcohol-metabolizing enzymes on alcohol hypersensitivity and alcohol-related health problems in Orientals. Environ Hlth Prev Med 1:1–8.
Takeshita T, Morimoto K, Mao XQ, Hashimoto T, Furuyama J, Furyuama J (1993). Phenotypic differences in low Km aldehyde dehydrogenase in Japanese workers. Lancet 341:837–838.
Takeshita T, Morimoto K, Mao X, Hashimoto T, Furuyama J (1994). Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population. Hum Genet 94:217–223.[ISI][Medline]
Takeshita T, Yang X, Inoue Y, Sato S, Morimoto K (2000). Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese. Cancer Lett 149:69–76.[ISI][Medline]
Tezal M, Grossi SG, Ho AW, Genco RJ (2001). The effect of alcohol consumption on periodontal disease. J Periodontol 72:183–189.[ISI][Medline]
Wickramasinghe SN, Gardner B, Barden G (1986). Cytotoxic protein molecules generated as a consequence of ethanol metabolism in vitro and in vivo. Lancet II:823–826.
Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ (1988). Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics 2:209–214.[Medline]
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