Effect of abatacept on the immunogenicity of 23-valent pneumococcal polysaccharide vaccination (PPSV23) in rheumatoid arthritis patients.

INTRODUCTION: Patients with rheumatoid arthritis (RA) treated with abatacept (ABT) are at increased risk for vaccine-preventable infections. The aim of the present study is to evaluate the humoral response to 23-valent pneumococcal polysaccharide (PPSV23) vaccination in RA patients receiving ABT. METHODS: The immunogenicity study was nested within a randomized, double-blind placebo-controlled study, designed to evaluate the efficacy of the PPSV23. PPSV23 was given to 111 RA patients, who were classified into three groups: RA control (n = 35), methotrexate (MTX) alone (n = 55), and ABT (n = 21). Before and 4-6 weeks after vaccination, we measured the patients' concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI). RESULTS: The pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups. CONCLUSIONS: OI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

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 glutathion S-transferase A1 polymorphism and susceptibility to urothelial cancer in the Japanese population.

GSTA1 has been reported to be most efficient in detoxifying N-acetoxy PhIP. In this study, 341 Japanese urothelial cancer patients and 457 healthy controls were compared for frequencies of GSTA1 genotype. We present the first evidence of an association between GSTA1*B (-567G, -69T, -52A) and urothelial cancer among never smokers. The frequency of GSTA1 *A/*B or *B/*B genotype was 24.3% in urothelial cancer cases, compared with 21.2% in the control groups (OR=1.22; 95%CI 0.87-1.72) after adjustment for age, gender and smoking status. But among never smokers, the GSTA1 *A/*B or *B/*B genotype was significantly higher in urothelial cancer cases (31.2%) compared with the controls (19.9%) (OR=1.73; 95%CI 1.01-2.97). This study suggests that exposure to food-derived PhIP could be one of the risk factors in the incidence of urothelial cancer in never smokers.

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.

Human glutathione S-transferase A1, T1, M1, and P1 polymorphisms and susceptibility to prostate cancer in the Japanese population.

PURPOSE: The incidence of prostate cancer is increasing in low-risk populations such as Japanese. One of the causes of this increase is considered to be associated with the Western diet, especially the high intake of red meat and fat. Glutathione S-transferase (GST) A1, T1, M1, and P1 are phase II enzymes that are important for activation and detoxification of chemical carcinogens. METHODS: In this study, 190 Japanese male patients with prostate cancer and 294 healthy controls, frequency-matched for age, were compared for frequencies of GSTA1, GSTT1, GSTM1, and GSTP1 genotypes. RESULTS: Among smokers, the frequency of the GSTA1*A/*B or *B/*B genotype in patients with prostate cancer (27.8%) showed a statistically significant increase compared with the control group frequency (18.2%; odds ratio [OR] =1.72; 95% CI, 1.01-2.94). In addition, the frequency of GSTT1 nondeletion genotype was associated with prostate cancer among smokers (OR =1.68; 95% CI, 1.06-2.68). The OR of carrying the combined genotyping of GSTA1*A/*B or *B/*B and GSTT1 nondeletion was 2.08 (95% CI, 1.14-3.80) with the combined genotyping of GSTA1*A/*A and GSTT1 null as a reference. On the other hand, no significant associations were observed for genotypes of GSTM1 and GSTP1 I105V. CONCLUSIONS: These findings suggest that the GSTA1 and GSTT1 polymorphisms are associated with prostate cancer susceptibility, especially among smokers.

Lack of evidence for the association of E-cadherin gene polymorphism with increased risk or progression of prostate cancer.

BACKGROUND: E-cadherin is an epithelial cell adhesion molecule, and decreased E-cadherin expression in human prostate cancer is associated with tumor grade and advanced clinical stage. A -160 C-->A polymorphism in the promoter region of E-cadherin has been shown to decrease gene transcription. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic disease. MATERIALS AND METHODS: We studied the effect of E-cadherin gene polymorphism on prostate cancer susceptibility in a case control study of 219 prostate cancer patients and 219 male controls, to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. RESULTS: The genotype frequencies in the prostate cancer group were C/C: 0.607, C/A: 0.352, A/A: 0.041, and in the control group C/C: 0.671, C/A: 0.301, A/A: 0.027. A significant difference between the two groups was not found (p = 0.34), and the adjusted OR for A/A genotype was not statistically significant (OR = 1.66, 95% CI 0.58-4.78). Subdividing prostate cancer according to tumor differentiation and stage, we found no association between E-cadherin polymorphism and poor differentiation and invasiveness of prostate cancer. CONCLUSIONS: These data do not support an association between the E-cadherin genotype and the occurrence or progression of prostate cancer in Japanese populations.