Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma

Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (-554 G>C, - 431A>C and - 225 G>C) in the MBL2 promoter were genotyped, and serum MBL levels were determined by enzyme-linked immunosorbent assay. Functional variabilities in the promoter polymorphisms were analyzed by a luciferase reporter assay and electrophoretic mobility shift assay (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA carrying ht2 [CAG] had significantly lower PC20 methacholine levels (P<0.001) than the non-carriers. The serum MBL levels were significantly higher in the DI-exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028). Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2 [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a - 554G probe produced a specific shifted band compared with the - 554C probe. These findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2 gene may increase susceptibility to the development of DI-OA in DI-exposed individuals.

Diagnostic Patterns in the Evaluation of Patients Presenting with Syncope at the Emergency or Outpatient Department

PURPOSE: Patterns of syncope evaluation vary widely among physicians and hospitals. The aim of this study was to assess current diagnostic patterns and medical costs in the evaluation of patients presenting with syncope at the emergency department (ED) or the outpatient department (OPD) of a referral hospital. MATERIALS AND METHODS: This study included 171 consecutive patients with syncope, who visited the ED or OPD between January 2009 and July 2009. RESULTS: The ED group had fewer episodes of syncope [2 (1-2) vs. 2 (1-5), p=0.014] and fewer prodromal symptoms (81.5% vs. 93.3%, p=0.018) than the OPD group. Diagnostic tests were more frequently performed in the ED group than in the OPD group (6.2+/-1.7 vs. 5.3+/-2.0; p=0.012). In addition, tests with low diagnostic yields were more frequently used in the ED group than in the OPD group. The total cost of syncope evaluation per patient was higher in the ED group than in the OPD group [823000 (440000-1408000) won vs. 420000 (186000-766000) won, p<0.001]. CONCLUSION: There were some differences in the clinical characteristics of patients and diagnostic patterns in the evaluation of syncope between the ED and the OPD groups. Therefore, a selective diagnostic approach according to the presentation site is needed to improve diagnostic yields and to reduce the time and costs of evaluation of syncope.

Gender-specific Association between Polymorphism of Vascular Endothelial Growth Factor (VEGF 936C>T) Gene and Patients with Stomach Cancer

PURPOSE: Angiogenesis plays an important role in the growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the present case-control study to determine whether there is an association between the VEGF 936C>T polymorphism and stomach cancer. PATIENTS AND METHODS: The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene with stomach cancer development was evaluated in a case-control study of 154 Korean stomach cancer patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Our results revealed significant association of T allele-bearing genotypes with increased risk for stomach cancer development. Genotype frequencies of the VEGF 936C>T polymorphisms were significantly different between patient and control groups (CT, AOR: 2.007, 95% CI: 1.277-3.156, TT, AOR: 4.790, 95% CI: 1.174-19.539, CT+TT, AOR: 2.147, 95% CI: 1.382-3.337). When stratified by gender and age, genotype frequencies were significantly different for stomach cancer in women and in patients younger than 55 years (in women, CT, OR: 3.049, 95% CI: 1.568-5.930, CT+TT, OR: 3.132, 95% CI: 1.638-5.990; in T polymorphism is a susceptibility factor for stomach cancer, at least in Korean. These observations, however, require further confirmation by a larger multi-ethnic study.

Polymorphism of the 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene and Microsatellite Instability (MSI) in Mucinous Colorectal Cancer

PURPOSE: Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc. METHODS: From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses. RESULTS: MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups. CONCLUSIONS: The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.

The Effect of Folic Acid to the Level of Homocysteine and Analysis of the Factors in Epilepsy Patients / 대한간질학회지

BACKGROUND: Folic acid has been frequently used for hyperhomocyesteinemia in various diseases and decreases the level of homocysteine. OBJECTIVES: To assess the effect of folic acid in the level of homocysteine in epilepsy patients, and to analyze factors affecting its responsiveness and the difference of its efficacy according to methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: Total 75 epilepsy patients with antiepileptic drugs (AEDs) therapy were included. 41 patients had normal level of homocysteine and 34 patients with hyperhomocysteinemia (> or =12 micro mol/ ) were supplemented with folic acid for 1 year. Thirty-four patients with hyperhomocyteinemia were divided into two groups according to the responsiveness of homocysteine to folic acid; decrease group (DG) and non-decrease group (NDG). RESULTS: The level of homocysteine in patients with hyperhomocysteinemia was significantly decreased after administration of folic acid, comparing with patients with normal level. DG was younger and had more male gender, shorter duration of seizure, and initial higher homocysteine level, compared to NDG (p<0.05). Patients with mutant type of MTHFR (CT+TT) had more decreased homocysteine level after supplement of folic acid, but had more increased homocysteine level without supplement of folic acid. Comparing between MTHFR genotypes, TT type had the most decreased homocysteine level than others, but there was no significance. CONCLUSION: Folic acid is useful treatment of hyperhomocysteinemia in epilepsy patients and the supplement of folic acid might be considered in patients with mutant type of MTHFR regardless of homocysteine level. The effect of folic acid supplement is greater in younger age, male sex, shorter duration of seizure, and initial higher homocysteine level.