Differential effects of aging, drinking and exercise on serum cholesterol levels dependent on the PPARA-V227A polymorphism.

Peroxisome proliferator-activated receptor alpha (PPARA alpha) plays a pivotal role in lipid metabolism. Our previous study reported that PPARA-V227A was a major polymorphism in Japanese, which was associated with markedly lower serum total cholesterol (TC) levels, which were significantly affected by alcohol drinking compared to subjects with the wild-type (PPARA-WT) allele. However, serum lipids are also associated with aging and exercise frequency. The objective of the present study was to evaluate the relationship between PPARA-V227A and these factors. Genetic analysis of the polymorphism was performed in 1058 Japanese men and 281 women, and the relationship with aging, drinking and exercise on serum lipids was analyzed in 989 men and 245 women after exclusion criteria had been applied. In men, drinking increased high-density lipoprotein cholesterol (HDL-C) levels in both PPARA-WT and A227 carriers, but to a significantly higher degree in the latter. In women, TC and low-density lipoprotein cholesterol (LDL-C) levels in the A227 carriers drinking at least once a week were significantly higher than in PPARA-WT carriers. TC and LDL-C levels in males with PPARA-WT increased with aging regardless of drinking habit, while LDL-C levels in the A227 drinking carriers were significantly lower in 45-yr-old or older subjects than in 35- to 45-yr-olds. In addition, no effect of exercising was observed in the A227 carriers, while increase in the HDL-C of the PPARA-WT carriers was exercise frequency dependent. These results suggest that the influence of drinking, aging or exercise on TC, LDL-C and HDL-C levels in the A227 carriers may be different from those in the PPARA-WT subjects.

Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas.

BACKGROUND: To reduce this complication and to enhance the radiation effect to hypoxic cells of high-grade gliomas, the authors performed noninvasive fractionated stereotactic radiotherapy (FSRT) using a Gamma unit combined with hyperbaric oxygen (HBO) therapy for the treatment of recurrent disease. PATIENTS AND METHODS: Twenty-five consecutive patients who had previously received radiotherapy with chemotherapy for recurrent high-grade gliomas, including 14 patients with anaplastic astrocytoma (AA) and 11 with glioblastoma multiforme (GBM), underwent Gamma FSRT immediately after HBO therapy (2.5 atmospheres absolute for 60 min). The Gamma FSRT was repeatedly performed using a relocatable head cast. Median tumor volume was 8.7 cc (range, 1.7-159.3 cc), and the median total radiation dose was 22 Gy (range, 18-27 Gy) to the tumor margin in 8 fractions. RESULTS: Actuarial median survival time after FSRT was 19 months for patients with AA and 11 months for patients with GBM, which was significantly different (P = 0.012, log-rank test). Two patients underwent subsequent second FSRT for regional or remote recurrence. Seven patients (28%) underwent subsequent craniotomies and resections at a mean of 8.4 months after FSRT treatment, and 4 of them had radiation effects without viable cells and remained alive for 50-78 months. CONCLUSION: Gamma FSRT after HBO therapy appears to confer a survival benefit for patients with recurrent high-grade gliomas and warrants further investigation.

Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis.

AIM: To examine the influence of lipoprotein lipase (LPL) gene polymorphism in ulcerative colitis (UC) patients. METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind III and Pvu II polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing. Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls. RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR = 3.13, 95% CI = 0.95-10.33). Patients with H(+/-) or H(-/-) genotype for Hind III polymorphism also were more numerous than those with H(+/+) genotype (OR = 2.51, 95% CI = 0.85-7.45). In the group with H(+/+) genotype for Hind III polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H(+/-) or H(-/-) genotype (P < 0.01, OR = 6.46, 95% CI = 1.39-30.12). Hypertriglycemia was also more prevalent in patients with P(+/+) genotypes for Pvu II polymorphism (P < 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls. CONCLUSION: Ser447stop and Hind III LPL polymorphisms may influence age of onset of UC, while Hind III and Pvu II polymorphisms influence serum triglyceride in UC patients.

Application of aldehyde dehydrogenase 2 (ALDH2) genetic diagnosis in support of decreasing alcohol intake.

Encouraging behavioral changes to decrease alcohol intake is not easy from the standpoint of health support. This study was conducted to examine whether the genetic diagnosis of ALDH2 polymorphism is useful in supporting those who want to decrease their alcohol intake. The participants in this study were 329 male employees who wanted to know the result of their ALDH2 genotype. We divided the 329 participants randomly into two groups. One was the "notified group" (n=157), and the other was the "non-notified group" (n=172). The subjects belonging to the "notified group" were informed of the results of the ALDH2 genotype diagnosis in April, 2003. Drinking habits and laboratory data were obtained before and after notification of the ALDH2 genotype. Among those with genotype ALDH2*1/*1, there was no significant change in drinking frequencies, nor was there any significant decline in liver function laboratory data in either of the groups before and after notification of the genotype. However, weekly alcohol intake tended to increase compared to that before notification. On the other hand, with regard to those with genotype ALDH2*1/*2, no significant changes in drinking frequencies or liver function laboratory data were evident in either group before and after notification of the genotype. However, the weekly alcohol intake tended to increase in the non-notified group, whereas it tended to decrease in the notified group. Although the result was not significant, it is suggested that, with further study and an increased sample size, the genetic diagnosis may be found to be useful.

[Relationship of changes in radius bone mineral density during seven years in working women around thirty years old with lifestyle, body measurement data and laboratory data].

OBJECTIVES: A longitudinal study was conducted to investigate the relationships of the change in radius bone mineral density for seven years with lifestyle, body measurement data and laboratory data. METHODS: The subjects of this study were 191 female employees working in an LSI manufacturing factory in Japan. Bone mineral density was measured on the radius of their nondominant side using DXA (dual energy X-ray absorptiometry) in 1995 and 2002. Other medical examinations were performed at the same time. Multiple regression analysis was also performed with the change in radius bone mineral density as the dependent variable. RESULTS: As a result of the multiple regression analysis, a significant positive correlation was observed between the change in body mass index (BMI) and the change in bone mineral density among the subjects aged 30 years and over and those under 30 years. A significant positive correlation was observed between daily milk intake and the change in bone mineral density among those aged under 30 years. A significant negative correlation was observed between daily alcohol intake and the change in bone mineral density among those aged under 30 years, and also between parity and the change in bone mineral density among those aged 30 years and over. CONCLUSIONS: BMI, parity, daily milk intake and daily alcohol intake are considered as significant factors that contribute to a change in bone mineral density. It is necessary that the recommended timing for medical examination be set according to age, and that a well-balanced guidance be provided from young adulthood.

[Consciousness survey regarding genetic diagnosis of glutathione S-transferase M1 (GSTM1) and aldehyde dehydrogenase 2 (ALDH2) polymorphism].

A Consciousness survey regarding genetic diagnosis of GSTM1 and ALDH2 was performed to evaluate the potential use of such a diagnosis in supporting those wanting to stop smoking and decrease alcohol intake. A questionnaire was given to 1,654 employees (male: 1,225, female: 429) who worked at an LSI manufacturing factory, and 1,434/1,654 (86.7%) responded to the survey. The number of respondents who replied that they "wanted to know the results of the genetic diagnosis of GSTM1 and ALDH2" were 731/1,401 (52.2%) and 812/1,434 (56.6%), respectively while the numbers of respondents who replied that they "did not want to know the results" were 138/1,401 (9.9%) and 103/1,434 (7.2%), respectively. The main reasons given for wanting to know the results of the genetic diagnosis of their enzymes reflected the respondents' awareness of their genetic susceptibility. These reasons included a desire to know the effects of tobacco smoke, to prevent diseases in the future, to know the effects of passive smoking or to know their tolerance for alcohol. On the other hand, the main reason for not wanting to know the genetic results that the respondents had no intention of stopping smoking and heavy drinking, or that they would be unable to stop even if they knew the results of the genetic diagnosis. Multiple regression analysis showed that the number of respondents who "wanted to know the results of the genetic diagnosis" was significantly higher among those respondents who are current smokers (male: OR = 1.66 95%CI 1.29-2.14, female: OR = 2.33 95%CI 1.37-3.98), those who understood the relationship between smoking and lung cancer (male: OR = 1.81 95%CI 1.25-2.63, female: OR = 2.77 95%CI 1.42-5.40) and those who with a high CAGE test score (male: OR = 1.96 95%CI 1.42-2.68, female: OR = 2.52 95%CI 1.07-5.94). The results of this survey suggest that genetic diagnosis of GSTM1 and ALDH2 polymorphism may be useful in supporting those who want to stop smoking and decrease their alcohol intake.

Human Glutathione S-transferase A1 polymorphism and susceptibility to oral squamous cell carcinoma in Japanese.

OBJECTIVES: Glutathione S-transferase (GST) A1 catalyses the activated heterocyclic aromatic a mine carcinogenN-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OAc-PhIP). This case-control study was carried out to examine whether the genetic polymorphism of GSTA1 is associated with the risk oforal squamous cell carcinoma among Japanese people in relation to their smoking status. METHODS: In this study, 97 Japanese oral squamous cell carcinoma patients and 457 healthy controls were compared for the frequencies of theGSTA1 genotypes ((*) A:-567T,-69C,-52G,(*) B:-567G,-69T,-52A). RESULTS: The frequencies ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were 32.3% in male cancer patients and 11.4% in female cancer patients, compared with 20.1% in the male control group (Odds ratio (OR)=1.86; 95% confidence interval (CI) 0.99-3.46) and 23.1% in the female control group (OR=0.58; 95% CI 0.18-1.81). TheGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were associated with an 86% increased risk of oral squamous cell carcinoma among males, albeit without statistical significance. Also, among male smokers, the frequency ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes was significantly higher among the oral squamous cell carcinoma patients (33.3%) than among the controls (19.6%). The OR of the male smokers with theGSTA1 (*)A/(*)B+(*)B/(*) B genotypes for oral squamous cell carcinoma was 1.97 (95% CI 1.02-3.79). CONCLUSIONS: We present the first evidence of an association betweenGSTA1 (*) B and oral squamous cell carcinoma among smokers. This study suggests that the GSTA1 polymorphism and tobacco smoke-derived PhIP are associated with oral squamous cell carcinoma susceptibility among male smokers.