Promoter Polymorphism (-308G/A) of Tumor Necrosis Factor-Alpha (TNF-α) Gene and Asthma Risk: An Updated Meta-Analysis.

Background and Aims: The relationship between the promoter polymorphism (-308G/A) of the tumor necrosis factor-alpha (TNF-α) gene and the susceptibility to asthma has been tested in several studies. However, the results have been inconsistent. Therefore, we performed an updated meta-analysis to evaluate the relationship between this promoter polymorphism of the TNF-α gene and the risk of asthma. Methods: Fifty case-control studies were included in this meta-analysis which provided 17,937 controls and 9961 asthma patients. The pooled p-value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association of this polymorphism of the TNF-α gene with the risk of asthma. The meta-analysis was carried out by Comprehensive Meta-Analysis software. Results: The results of our meta-analysis revealed that the TNF-α polymorphism (-308, G/A) was strongly associated with the risk of asthma (p < 0.05 in the allelic, dominant, and recessive models, respectively). In further analyses, based on age group and ethnicity, we observed this association for all subpopulations examined (p < 0.05 in allelic, dominant, and recessive models, respectively). Conclusion: This large-scale meta-analysis supports a strong association between the TNF-α gene promoter polymorphism (-308G/A) and the development to asthma in both children and adults.

The Effects of Korea Red Ginseng on Inflammatory Cytokines and Apoptosis in Rat Model with Chronic Nonbacterial Prostatitis.

Chronic prostatitis typically occurs in aging men, and its symptoms include frequent and painful urination. In recent study, several studies have shown that Korean red ginseng (KRG) can be used in the prevention and treatment of various diseases. The objective of this study is to investigate whether KRG can play a role in repressing the development of chronic nonbacterial prostatitis (CNP) in male Wistar rats. To induce CNP, rats were castrated and beta-estradiol (0.25 mg/kg) was subcutaneously (s.c.) injected daily. 7-week-old male Wistar rats were divided into 5 groups (the normal group, CNP group, positive group, and KRG group (0.25g/kg) and another KRG (0.50g/kg) group. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed. Compared to the positive group, the KRG groups (0.25g/kg and 0.50g/kg) showed similar protective properties on CNP based on the histopathologic morphology of the prostate and the inflammation cytokines in the prostate tissue. Also, results of the immunohistochemistry staining showed that expression levels of vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), interleukin 1 beta (IL-1ß), tumor necrosis factor (TNF-alpha), and cytochrome c oxidase subunit II (COX2) were also decreased in KRG group (0.25g/kg) and KRG group (0.50g/kg). These results suggested that KRG inhibited the development of CNP and might a useful herbal treatment or functional food for CNP.

Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk: updated meta-analysis.

Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been reported to have a relationship with the risk of the development of various cancers. Many studies have described the influence of Ser326Cys polymorphism of the hOGG1 gene on cancer susceptibility. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the relationship between the hOGG1 polymorphism and the development of cancer.Electronic databases including PubMed, Embase, Google Scholar, and the Korean Studies Information Service System (KISS) were searched. The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to assess the strength of the association with the risk of cancer using Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies including 38,757 cancer patients and 50,177 control subjects were analyzed for the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys polymorphism of the hOGG1 gene statistically increased the susceptibility of cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR = 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI = 1.033-1.179, p = 0.002). Also, other genotype models showed significant association with cancer (p < 0.05, respectively).The present meta-analysis concluded that the G allele was associated with an increased risk of cancer. It suggested that the hOGG1 polymorphism may be a candidate marker of cancer.

Association of promoter polymorphism -857C/T (rs1799724) in tumor necrosis factor gene with intracerebral hemorrhage in Korean males.

BACKGROUND AND PURPOSE: Tumor necrosis factor (TNF) has been shown to be involved in the pathogenesis of hemorrhagic stroke, having deleterious effects on cerebral arteries by promoting inflammation and apoptosis in vascular and immune cells. In this study, we investigated genetic association between TNF gene and intracerebral hemorrhage (ICH) in a Korean population. METHODS: Single nucleotide polymorphisms (SNPs) of TNF gene [-857C/T (rs1799724) and -308G/A (rs1800629)] were selected and genotyped using direct sequencing in 144 ICH patients and 455 control subjects. Genotype distribution and allele frequency were compared between cases and controls using logistic regression. RESULTS: -857C/T was significantly associated with ICH in log-additive [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.14-2.24, p = 0.0081], and recessive models (OR = 3.25, 95% CI = 1.28-8.27, p = 0.016). The frequency of the -857TT genotype increased in ICH patients. Allele frequency analysis also showed that the -857T allele was associated with an increased risk of ICH (OR = 1.62, 95% CI = 1.15-2.30, p = 0.006). In the analysis according to the gender, we found that the association of -857C/T was gender-different. The -857C/T was significantly associated with ICH only in males (OR = 1.99, 95% CI = 1.24-3.19, p = 0.0043 in males; OR = 1.30, 95% CI = 0.76-2.22, p = 0.34 in females). CONCLUSION: These results suggest that promoter polymorphism of TNF gene, -857C/T, may be involved in the susceptibility of ICH in males.

Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis.

BACKGROUND Ischemic stroke and myocardial infarction are fatal diseases and are among the top 10 causes of death in Korea, including arterial thromboembolic events. Many previous studies have described the function of interleukin-6 (IL-6) in arterial thromboembolic events and the association between promoter single-nucleotide polymorphism (SNP) (rs1800795; -174, G/C) of the IL-6 gene. However, these results were controversial. Therefore, we performed a meta-analysis to more precisely assess the association between the SNP of the IL-6 gene and susceptibility to arterial thromboembolic events. MATERIAL AND METHODS We used PubMed, Embase, Google Scholar, and Korean Studies Information Service System (KISS) electronic databases. Comprehensive Meta-analysis software (Corporation, NJ) was used to evaluate the relationship between rs1800795 SNP of IL-6 gene and risk of arterial thromboembolic events. Odds ratio (OR), 95% confidence interval (CI), and P value were also calculated. The 13 eligible studies were analyzed in the meta-analysis. RESULTS The present meta-analysis found that rs1800795 SNP of IL-6 gene is not significantly associated with susceptibility to arterial thromboembolic events (C allele vs. G allele, OR=1.04, 95% CI=0.91-1.19, P=0.619; CC vs. CG+GG, OR=1.09, 95% CI=0.91-1.31, P=0.364; CC+CG vs. GG, OR=0.97, 95% CI=0.78-1.21, P=0.763, respectively), and the SNP of IL-6 gene also did not show any significant association with ischemic stroke or myocardial infarction (P>0.05 in each model). CONCLUSIONS We found that rs1800795 SNP of IL-6 gene was not related to arterial thromboembolic events. However, further study will be needed to confirm these results.

Association Study of Polymorphisms of Epidermal Growth Factor and Epidermal Growth Factor Receptor With Benign Prostatic Hyperplasia in a Korean Population.

PURPOSE: Recent studies have suggested that specific single-nucleotide polymorphisms (SNPs) contribute to the clinical features of benign prostatic hyperplasia (BPH). In this study, we investigated the relationships of genetic polymorphisms of the epidermal growth factor (EGF) gene and the epidermal growth factor receptor (EGFR) gene with BPH. METHODS: A total of 218 patients with BPH were enrolled in this study. We evaluated the relationship between eight SNPs in the EGF and EGFR genes and prostate volume, prostate-specific antigen (PSA), and International Prostate Symptom Score of BPH patients. Each SNP was genotyped by direct sequencing. Statistical analysis applying codominant, dominant, recessive, and log-additive models was performed via logistic regression. RESULTS: The rs11568943 and rs11569017 SNPs in the EGF gene showed significant associations with prostate volume (rs11568943: P=0.038 in the log-additive model, P=0.024 in the allele distribution; rs11569017, P=0.031 in the dominant model, P=0.028 in the log-additive model, P=0.020 in the allele distribution). Additionally, the rs3756261, rs11568943, and rs11569017 SNPs of the EGF gene and the rs2293347 SNP of the EGFR gene were associated with PSA levels (P<0.05 in each model, respectively). CONCLUSIONS: These results suggest that the EGF gene may affect prostate volume. In addition, the EGF and EGFR genes may be associated with PSA levels in patients with BPH.

Association between polymorphisms of estrogen receptor 2 and benign prostatic hyperplasia.

Estrogens and estrogen receptors (ESRs) have been implicated in the stimulation of aberrant prostate growth and the development of prostate diseases. The aim of the present study was to investigate four single nucleotide polymorphisms (SNPs) of the ESR2 gene in order to examine whether ESR2 is a susceptibility gene for benign prostatic hyperplasia (BPH). In order to evaluate whether an association exists between ESR2 and BPH risk, four polymorphisms [rs4986938 (intron), rs17766755 (intron), rs12435857 (intron) and rs1256049 (Val328Val)] of the ESR2 gene were genotyped by direct sequencing. A total of 94 patients with BPH and 79 control subjects were examined. SNPStats and Haploview version 4.2 we used for the genetic analysis. Multiple logistic regression models (codominant1, codominant2, dominant, recessive and log-additive) were produced in order to obtain the odds ratio, 95% confidence interval and P-value. Three SNPs (rs4986938, rs17766755 and rs12435857) showed significant associations with BPH (rs4986938, P=0.015 in log-additive model; rs17766755, P=0.033 in codominant1 model, P=0.019 in dominant model and P=0.020 in log-additive model; rs12435857, P=0.023 in dominant model and P=0.011 in log-additive model). The minor alleles of these SNPs increased the risk of BPH, and the AAC haplotype showed significant association with BPH (χ2=6.34, P=0.0118). These data suggest that the ESR2 gene may be associated with susceptibility to BPH.

Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model.

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the common male diseases, which is provoked by dihydrotestosterone (DHT) and androgen signals. Several studies showed that curcumin has various effects of prevention and treatment to diseases. We investigated whether curcumin may repress the development of BPH in male Wistar rats. METHODS: Seven weeks male Wistar rats were and divided into 4 groups (normal group, BPH group, finasteride group, curcumin group; n = 8 for each group). In order to induce BPH in rats, rats were castrated and testosterone was injected subcutaneously everyday (s.c., 20 mg/kg). Rats in the curcumin group were treated 50 mg/kg, administered orally for 4 weeks. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed. RESULTS: Compared to the finasteride group as positive group, the curcumin group showed similarly protective effect on BPH in histopathologic morphology, prostate volume. Results of immunohistochemistry and western-blot showed decreased expressions of VEGF, TGF-ß1, and IGF1 were also decreased in the curcumin group. CONCLUSIONS: These results suggested that curcumin inhibited the development of BPH and might a useful herbal treatment or functional food for BPH.

Transforming growth factor-ß receptor 2 gene polymorphisms are associated with end-stage renal disease.

BACKGROUND: Transforming growth factor-beta (TGF-ß) is a multifunctional cytokine involved in immune disorders, cancer, asthma, lung fibrosis, and chronic kidney disease, and its signal pathways are considered crucial mediators of a variety of cellular processes. In addition, several recent studies have reported that TGF-ß receptor (TGF-ßR) gene polymorphism is associated with chronic kidney disease. However, the association between end-stage renal disease (ESRD) and the TGF-ß gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the TGF-ß ligands or their receptors may be related to ESRD. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the TGF-ßR2 and TGF-ß2 genes and ESRD, in 312 patients with ESRD and 258 controls. RESULTS: Compared with the control participants, the frequencies of the TGF-ßR2 (rs764522(⁎)C) and TGF-ßR2 (rs3087465(⁎)G) alleles were significantly higher in the patients with ESRD. Genotyping analysis demonstrated that two SNPs in TGF-ßR2 of the four SNPs included in the study were significantly associated with ESRD in the codominant 1 [rs764522, odds ratio (OR)=1.65; rs3087465, OR=1.63], dominant (rs764522, OR=1.63; rs3087465, OR=1.57), and log-additive (rs764522, OR=1.54; rs3087465, OR=1.39) models after adjusting for age and sex. CONCLUSION: We suggest that TGF-ßR2 polymorphisms (rs764522 and rs3087465) increase the risk of development of ESRD.

Single nucleotide polymorphisms of the Fas gene are associated with papillary thyroid cancer.

OBJECTIVES: Fas is the prototypic representative of the death receptor subgroup of the tumor necrosis factor (TNF) receptor family. Recently, single nucleotide polymorphisms (SNPs) of the Fas or Fas ligand (FasL) genes have been shown to be associated with an increased risk of several cancers and with the prognosis of several cancers. The objective of this study was to evaluate the association between the SNPs of the Fas and FasL genes and papillary thyroid cancer (PTC) and to assess the relationship between these SNPs and the clinicopathological characteristics of PTC. METHODS: Five SNPs located within the two genes of Fas and FasL were genotyped using direct sequencing in 94 patients with PTC and 364 healthy controls. Genetic data were analyzed using commercially available software. And, the statistical analyses were performed according to clinicopathologic characteristics of PTC. RESULTS: Genotyping analysis demonstrated that the intron SNP (rs1571013), promoter SNP (rs1800682) and 3'-UTR SNP (rs1468063) of Fas were significantly associated with the development of PTC. We also detected a significant difference between patients with PTC and healthy controls with respect to Fas gene allele frequencies. Furthermore, we found that the 3'-UTR SNP (rs1468063) of Fas was associated with the multifocality of cancer [dominant model, OR 0.28, p=0.028; log-additive model, OR 0.43, p=0.033]. CONCLUSION: We observed a significant association between SNPs of the Fas gene and the development of PTC. In addition, there was a significant association between a Fas SNP and the multifocality of PTC.

Meta-analysis of association of the matrix metalloproteinase 2 (-735 C/T) polymorphism with cancer risk.

The association between matrix metalloproteinase 2 (MMP2) gene polymorphisms and cancer risk has been investigated in many published studies; however, the currently available results are inconclusive. Therefore, we performed a meta-analysis to provide conclusive evidence for an association between the MMP2 polymorphism (-735 C/T) and cancer risk. Sixteen case-control studies with 11792 individuals were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the MMP2 polymorphism (-735 C/T) was not associated with cancer risk in any of the models. However, the subgroup analysis revealed that dominant model (C/T+T/T vs. C/C: OR=1.24, 95% CI=1.01-1.53) and codominant 1 model (C/T vs. C/C: OR=1.30, 95% CI=1.05-1.62) were significantly associated with cancer risk in the Caucasian population. In conclusion, our meta-analysis indicated that the MMP2 polymorphism (-735 C/T) might be genetic risk factor for the carcinogenesis in Caucasians. However, more studies with a larger sample size are needed to provide more precise evidence.

Association between interleukin 17/interleukin 17 receptor gene polymorphisms and papillary thyroid cancer in Korean population.

BACKGROUND: Although numerous recent studies have implicated a role for interleukin 17(IL17) in tumor development, the mechanisms of IL17 involvement are still uncharacterized. The aims of this study were to determine whether single nucleotide polymorphisms (SNPs) in IL17 and IL17R contribute to the development of papillary thyroid cancer (PTC) and to assess the relationship between IL17 and IL17R SNPs and the clinicopathologic characteristics of PTC. MATERIALS AND METHODS: Eight SNPs located within the IL17A, IL17RA, and IL17RB genes were genotyped using direct sequencing in 94 patients with PTC and 260 patients without PTC (controls). Genetic data were analyzed using commercially available software. Statistical analyses were then performed to examine the relationships between these SNPs and the clinicopathologic characteristics of PTC. RESULTS: Genotyping analysis demonstrated that the IL17RA SNP rs4819554 (codominant model 1, odds ratio (OR)=0.39, P=0.001) and the IL17RB SNP rs1025689 (dominant model, OR=0.59, P=0.043) were significantly associated with lack of PTC. Interestingly, the IL17A SNP rs2275913 (codominant model 2, OR=0.19, P=0.034) was significantly associated with lack of multifocality. Furthermore, the IL17RA SNP rs4819554 (dominant model, OR=0.25, P=0.010) was significantly associated with lack of cancer bilaterality. CONCLUSION: In this study of SNPs in the IL17 and IL17R genes in patients with PTC, we demonstrated that IL17RA polymorphisms can influence both the development and the bilaterality of PTC.

Association of FOS-like antigen 1 promoter polymorphism with podocyte foot process effacement in immunoglobulin A nephropathy patients.

BACKGROUND: FOS has been implicated in the progression of renal disease including IgAN. In this study, we investigated whether polymorphisms of FOS family genes [FOS, FOSB, FOS-like antigen 1 (FOSL1), and FOSL2] were associated with immunoglobulin A nephropathy (IgAN) and the clinical phenotypes of IgAN patients. METHODS: We genotyped single nucleotide polymorphisms (SNPs) of FOS family genes (rs2239615 and rs7101 for FOS, rs12373539 and rs2282695 for FOSB, rs637571 for FOSL1, and rs925255 for FOSL2) using direct sequencing in 198 IgAN patients and 290 control subjects. RESULTS: No SNPs were associated with IgAN; however, in the analysis of clinical phenotypes, we found that rs637571 of FOSL1 was associated with podocyte foot process effacement of IgAN in additive (CT vs. TT vs. CC, P = 0.0031, OR = 2.08, 95% CI = 1.27-3.40) and dominant models (CT/TT vs. CC, P = 0.0034, OR = 2.50, 95% CI = 1.35-4.64). The frequency of genotypes containing the T allele was increased in IgAN patients with podocyte foot process effacement, compared to those without podocyte foot process effacement. CONCLUSION: These results suggest that FOSL1 may be related to IgAN severity.

Association studies of cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene polymorphisms with acute rejection in kidney transplantation recipients.

Recent studies have shown that single-nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case-control association study in 63 AR and 284 non-AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0.023) and the use of tacrolimus (p = 0.017) were significantly different between the two groups. The use of mycophenolate mofetil (MMF) and antibody induction therapy was significantly lower in the AR group. Multiple logistic regression models (codominant, dominant, recessive, and log-additive models) adjusted by sex and type of immunosuppressive regimens were applied to determine the odds ratios (ORs), 95% confidence intervals (CIs), and p-values. The rs2515641 of CYP2E1 showed significant differences between the AR patient group and non-AR group (p = 0.003, OR = 2.55, 95% CI = 1.37-4.75 in the codominant 1 model; p = 0.002, OR = 2.61, 95% CI = 1.43-4.77 in the dominant model; p = 0.0035, OR = 2.13, 95% CI = 1.29-3.50 in the log-additive model). The allele of the rs2515641 SNP also showed a significant association (p = 0.004, OR = 1.99, 95% CI = 1.24-3.21). This study suggests that the CYP2E1 polymorphism may be related to the development of AR in Korean kidney transplantation recipients.

Association of BH3 interacting domain death agonist (BID) gene polymorphisms with proteinuria of immunoglobulin A nephropathy.

BACKGROUND: Apoptosis plays an important role in the mechanism regulating the development of glomerulonephritis. We investigated whether polymorphisms of apoptotic genes such as B-cell CLL/lymphoma 2 (BCL2), BH3-interacting domain death agonist (BID), and caspase 8 (CASP8) were associated with immunoglobulin A nephropathy (IgAN) and with the clinical phenotypes of IgAN patients. METHODS: We genotyped promoter and coding region single nucleotide polymorphisms (SNPs) (rs2279115 and rs1801018 for BCL2; rs8190315 and rs2072392 for BID; and rs6747918 and rs1045487 for CASP8) using direct sequencing in 195 IgAN patients and 289 control subjects. RESULTS: No SNPs were associated with IgAN. However, in analysis of clinical phenotypes, we found that rs8190315 and rs2072392 of BID were associated with proteinuria levels of IgAN patients in additive (AG vs. GG vs. AA, p = 0.0008 for rs8190315; TC vs. CC vs. TT, p = 0.0012 for rs2072392) and dominant models (AG/GG vs. AA, p = 0.0014 for rs8190315; TC/CC vs. TT, p = 0.0031 for rs2072392). In particular, the frequencies of genotypes containing minor alleles of rs8190315 (G allele) and rs2072392 (C allele) were increased in IgAN patients with higher protienuria levels (> 40 mg/m(2)/h). CONCLUSION: These results suggest that BID may play a role in severe IgAN.

Association Study of FOS-Like Antigen-2 Promoter Polymorphisms With Papillary Thyroid Cancer in Korean Population.

OBJECTIVES: FOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode leucine zipper proteins that can heterodimerize with proteins of Jun family. Thus, activating protein (AP)-1 transcription factor is formed, has a crucial role in proliferation, differentiation and apoptosis of normal tissue as well as oncogenic transformation and progression. We performed an association study of single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid cancer (PTC). We also estimated the relationships between the SNPs and the clinicopathologic characteristics of PTC. METHODS: One promoter SNPs (rs925255) of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213 controls. PTC patients were dichotomized and compared with respect to clinical parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer, SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the genetic effect with adjustment for age and sex. RESULTS: SNP (rs925255) in FOSL-2 showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34 to 0.91; P=0.02). But we fail to prove significant association between this polymorphism (rs925255) and clinico-pathological parameters. CONCLUSION: Our findings suggest that the rs925255 SNP and its allele G show significant association with the PTC in Korean population.

Association of BID SNPs (rs8190315 and rs2072392) and clinical features of benign prostate hyperplasia in Korean population.

Exercise has beneficial effect on cancer apoptosis and benign prostatic hyperplasia (BPH). The BH3 interacting domain death agonist (BID) gene expression is associated with apoptosis or cell proliferation. In this study, we investigated the association between BID single nucleotide polymorphisms (SNPs) and the development, prostate volume, and international prostate symptom score (IPSS) of BPH. In 222 BPH males and 214 controls, two SNPs in BID [rs8190315 (Ser56Gly), and rs2072392 (Asp106Asp)] were genotyped and analyzed using multiple logistic regression models. In the result, the genotype and allele frequencies of rs8190315 and rs2072392 were not associated with BPH development or IPSS, however, the allele frequencies [odd ratio (OR)= 1.90, 95% confidence interval (CI)= 1.07-3.41, P= 0.03] and genotype frequencies (in dominant model, OR= 1.94, 95% CI= 1.01-3.74, P= 0.42) of rs8190315, and the genotype frequencies of rs2072392 (in dominant model, OR= 1.94, 95% CI= 1.01-3.74, P= 0.42) were associated with increased prostate volume. We propose that rs8190315 and rs2072392 of BID may contribute to the disease severity of BPH.

Influence of Panax ginseng on Alpha-Adrenergic Receptor of Benign Prostatic Hyperplasia.

PURPOSE: Benign prostatic hyperplasia (BPH) is the most common prostate problem in older men. The present study aimed to investigate the inhibitory effect of Panax ginseng C.A. Meyer (P. ginseng) on a rat model of testosterone-induced BPH. METHODS: The rats were divided into 3 groups (each group, n=10): control, testosterone-induced BPH (20 mg/kg, subcutaneous injection), and P. ginseng (200 mg/kg, orally) groups. After 4 weeks, all animals were sacrificed to examine the blood biochemical profiles, prostate volume, weight, histopathological changes, alpha-1D adrenergic receptor (Adra1d) mRNA expression, and epidermal growth factor receptor (EGFR) and B-cell CLL/lymphoma 2 (BCL2) protein expression. RESULTS: The group treated with P. ginseng showed significantly lesser prostate size and weight than the testosterone-induced BPH group. In addition, P. ginseng decreased the mRNA expression of Adra1d as well as the expression of EGFR and BCL2 in prostate tissue. CONCLUSIONS: These results suggest that P. ginseng may inhibit the alpha-1-adrenergic receptor to suppress the development of BPH.

TXNDC5 gene polymorphism contributes to increased risk of hepatocellular carcinoma in the Korean male population.

Thioredoxin domain-containing protein-5 (TXNDC5) has been found to be associated with cancer development and growth. We investigated whether TXNDC5 gene polymorphisms are associated with hepatocellular carcinoma (HCC) in a Korean male population. Seven SNPs were selected based on minor allelic frequency (≥5%). The SNPs consisted of three exonic SNPs (rs8643, rs7764128 and rs1043784) and four intronic SNPs (rs1225944, rs1225943, rs1225945 and rs1225958). We selected and assessed these SNPs in 160 patients with HCC and 178 controls. Genetic data were analyzed using SNPAnalyzer Pro, SNPStats, and Haploview programs. Two SNPs of the TXNDC5 gene were found to be associated with the risk of HCC development. The genotypic frequency of rs1225944 was associated with HCC in the recessive model [CC/CT vs. TT, p=0.43, Fisher's exact test p=0.032; odds ratio (OR)=0.54, 95% confidence interval (CI)=0.11-2.71]. The genotypic frequency of rs1225943 was associated with HCC in the co-dominant 2 (AA vs. CC, p=0.07; Fisher's exact test p=0.001, OR=0.23, 95% CI=0.05-1.10), recessive (AA/AC vs. CC, p=0.044, Fisher's exact test p=0.001, OR=0.25, 95% CI=0.05-1.17), and log-additive models (p=0.08, Fisher's exact test p=0.002, OR=0.68, 95% CI=0.44-1.05). The haplotype CA and TC of rs1229544 and rs1225943, demonstrated a significant association with HCC. Our results suggest that TXNDC5 polymorphisms could be related to the development of HCC in the Korean male population.

Association study of chemokine (C-C motif) ligand 5 gene polymorphism and papillary thyroid cancer.

UNLABELLED: The association between polymorphism of CC chemokine ligand 5 (CCL5) and cancer has been reported in several studies, however, there is no data in papillary thyroid cancer (PTC). OBJECTIVES: The aim of this study was to investigate whether a promoter single nucleotide polymorphisms (SNP) in CCL5 contributes to the development of PTC and assess the relationships between the CCL5 SNP and the cliniopathologic characteristics of PTC. METHODS: One promoter SNP (rs2107538, -281C/T) in CCL5 was genotyped using direct sequencing in 93 PTC patients and 212 healthy controls. Genetic data were analyzed using SNPStats, Helixtree, and SNPAnalyzer. PTC patients were dichotomized and compared with respect to cliniopathologic characteristics of PTC. RESULTS: An association was evident between PTC and SNP (rs2107538) in CCL5 [codominant model 2 (T/T vs. C/C), OR = 2.74, 95% CI = 1.18-6.37, p = .019; dominant model, OR = 2.25, 95% CI = 1.01-5.03, p = .049; recessive model, OR = 1.73, 95% CI = 1.06-2.82, p = .030]. When the genetic relationships between SNP and subgroups of PTC patients were assessed, SNP rs2107538 in CCL5 was not associated with any clinicopathologic characteristics of PTC. CONCLUSIONS: SNP in the CCL5 -281 promoter gene could increase the risk of developing PTC in Koreans.