HbA1c and systolic blood pressure variation to predict all-cause mortality in patients with type 2 diabetes mellitus.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) variation or blood pressure (BP) variation was known to be an independent predictor of all-cause mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the combined effect of HbA1c and systolic blood pressure (SBP) variation on all-cause mortality and if there was a gender difference in patients with T2DM. METHODS: Patients with T2DM who had at least three HbA1c, SBP measurements within 12-24 months during 2001-2007 were included. Coefficient of variation (CV) was used to evaluate variation. The 75th percentile of HbA1c-CV and SBP-CV were set as a cutoff to define high and low variation. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazard models. RESULTS: A total of 2744 patients were included, of whom 769 died during the 11.7 observation years. The associated risk of all-cause mortality was 1.22 [1.01- 1.48], P = 0.044, for low HbA1c-CV & high SBP-CV; 1.28 [1.04-1.57], P = 0.020, for high HbA1c-CV & low SBP-CV; and 1.68 [1.31-2.17], P < 0.001, for high HbA1c-CV & high SBP-CV. The associated risk remained unchanged in either males or females older than 50 years old, although there is only numerically higher for high HbA1c-CV & low SBP-CV in females older than 50 years old. CONCLUSIONS: Both HbA1c and SBP variation were significant predictors of all-cause mortality in patients with T2DM. The combined effect was higher than either alone and no gender difference in patients older than 50 years old.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.

Thyroid diseases increased the risk of type 2 diabetes mellitus: A nation-wide cohort study.

Thyroid function may alter carbohydrate metabolism via influence of insulin, which may in terms of derangement of thyroid function and insulin function result in the development of type 2 diabetes mellitus (T2D). We investigated the association of thyroid disorders with T2D by a cohort study of the Taiwan nationwide health insurance database.A sub-dataset of the National Health Insurance Research Database (NHIRD) was used in this study. The thyroid disease (both hyper- and hypo-thyroidism) group was chosen from patients older than 18 years and newly diagnosed between 2000 and 2012. The control group consisted of randomly selected patients who never been diagnosed with thyroid disease and 4-fold size frequency matched with the thyroid disease group. The event of this cohort was T2D (ICD-9-CM 250.x1, 250.x2). Primary analysis was performed by comparing the thyroid disease group to the control group and the second analysis was performed by comparing the hyperthyroidism subgroup, hypothyroidism subgroup, and control group.The occurrence of T2D in the thyroid disease group was higher than the control group with hazard ratio (HR) of 1.23 [95% confidence interval (CI) = 1.16-1.31]. Both hyperthyroidism and hypothyroidism were significantly higher than control. Significantly higher HR was also seen in female patients, age category of 18 to 39-year-old (y/o) and 40 to 64 y/o subgroups. Higher occurrence of T2D was also seen in thyroid disease patients without comorbidity than in the control group with HR of 1.47 (95% CI = 1.34-1.60). The highest HR was found in the half-year follow-up.There was a relatively high risk of T2D development in patients with thyroid dysfunctions, especially in the period of 0.5 to 1 year after presentation of thyroid dysfunctions. The results suggest performing blood sugar tests in patients with thyroid diseases for early detection and treatment of T2D.

Susceptible gene of stasis-stagnation constitution from genome-wide association study related to cardiovascular disturbance and possible regulated traditional Chinese medicine.

BACKGROUND: This study identified susceptible loci related to the Yu-Zhi (YZ) constitution, which indicates stasis-stagnation, found in a genome-wide association study (GWAS) in patients with type 2 diabetes and possible regulated traditional Chinese medicine (TCM) using docking and molecular dynamics (MD) simulation. METHODS: Non-aboriginal Taiwanese with type 2 diabetes were recruited. Components of the YZ constitution were assessed by a self-reported questionnaire. Genome-wide SNP genotypes were obtained using the Illumina HumanHap550 platform. The world's largest TCM database ( http://tcm.cmu.edu.tw/ ) was employed to investigate potential compounds for PON2 interactions. RESULTS: The study involved 1,021 unrelated individuals with type 2 diabetes. Genotyping data were obtained from 947 of the 1,021 participants. The GWAS identified 22 susceptible single nucleotide polymorphisms on 13 regions of 11 chromosomes for the YZ constitution. Genotypic distribution showed that PON2 on chromosome 7 was most significantly associated with the risk of the YZ constitution. Docking and MD simulation indicated 13-hydroxy-(9E_11E)-octadecadienoic acid was the most stable TCM ligand. CONCLUSIONS: Risk loci occurred in PON2, which has antioxidant properties that might protect against atherosclerosis and hyperglycemia, showing it is a susceptible gene for the YZ constitution and possible regulation by 13-hydroxy-(9E_11E)-octadecadienoic acid.

The Relationship between Stasis-Stagnation Constitution and Peripheral Arterial Disease in Patients with Type 2 Diabetes.

Objectives. In traditional Chinese medicine, Yu-Zhi (YZ, indicating stasis and stagnation) constitution describes a body that tends to express abnormal circulatory conditions. This study identified the linkage between YZ constitution and peripheral arterial disease (PAD) in patients with type 2 diabetes. Methods. Patients over 20 years of age who had had type 2 diabetes for 5 years or longer were recruited. PAD was diagnosed if the ankle-brachial index score was ≤0.9 in either leg. Level of YZ constitution was accessed by an YZ Constitution Questionnaire. Results. A total of 712 patients (354 men and 358 women) with a mean age of 61.5 ± 10.6 years and diabetes duration of 13.1 ± 6.7 years were recruited. The prevalence of PAD among our patients was 7.2%. Multivariate logistic regression revealed significant correlations between PAD and, respectively, YZ score, age, diabetes duration, current smoking, and hs-CRP. Conclusion. In addition to traditional risk factors, YZ constitution was statistically associated with PAD in patients with type 2 diabetes. This result invites further research into the effectiveness of traditional Chinese medicine to treat YZ constitution.

The association between polymorphisms of B7 molecules (CD80 and CD86) and Graves' ophthalmopathy in a Taiwanese population.

OBJECTIVE: This study evaluates whether B7 molecules (CD80 and CD86) could be used as genetic markers for the development of Graves' ophthalmopathy (GO). DESIGN: Cross-sectional study. PARTICIPANTS: We included 471 patients with Graves' disease (GD; 200 patients with GO and 271 patients without GO) in a Chinese population in Taiwan. METHODS: An endocrinologist with substantial experience in thyroid diseases identified GO. Blood samples were taken for DNA extraction from GD subjects. The gene polymorphism of CD80 and CD86 was genotyped by polymerase chain reaction in each patient. MAIN OUTCOME MEASURES: Genotypes of CD80 and CD86 polymorphism. RESULTS: We found that the frequency of C allele at position rs_9831894 of the CD86 gene is different in patients with GD (with and without GO; chi-square test, P = 0.0017). In addition, the multifactor dimensionality reduction method was used to identify the best gene-gene interaction to predict the risk of GO. We identified an interaction between CD80_rs9289131 and CD86_rs9872483 (sign test, P = 0.0010). Moreover, the G-A haplotype was shown to have a protective effect in the development of ophthalmopathy among patients with GD (odds ratio, 0.63; 95% confidence interval, 0.44-0.90). Moreover, among patients with GO, the patients carrying the G-A haplotype had a lower level of free thyroxine T(4) than those not carrying the G-A haplotype (P = 0.0001). CONCLUSIONS: These results suggest that the polymorphisms of the CD86 gene may be used as genetic markers for making the diagnosis and prognosis of GO. Therefore, GO could be a disease with complex genetic factors, resulting from the existing gene-gene interaction found in the present study.

Toll-like receptor gene polymorphisms are associated with susceptibility to Graves' ophthalmopathy in Taiwan males.

BACKGROUND: Toll-like receptors (TLRs) are a family of pattern-recognition receptors, which plays a role in eliciting innate/adaptive immune responses and developing chronic inflammation. The polymorphisms of TLRs have been associated with the risk of various autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis and rheumatorid arthritis. The aim of this study was to evaluate whether TLR genes could be used as genetic markers for the development of Graves' ophthalmopathy (GO). METHODS: 6 TLR-4 and 2 TLR-9 gene polymorphisms in 471 GD patients (200 patients with GO and 271 patients without GO) from a Taiwan Chinese population were evaluated. RESULTS: No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-9 gene polymorphisms between the GD patients with and without GO. However, sex-stratified analyses showed that the association between TLR-9 gene polymorphism and GO phenotype was more pronounced in the male patients. The odds ratios (ORs) was 2.11 (95% confidence interval [CI] = 1.14-3.91) for rs187084 AàG polymorphism and 1.97 (95% CI = 1.07-3.62) for rs352140 AàG polymorphism among the male patients. Increasing one G allele of rs287084 and one A allele of rs352140 increased the risk of GO (p values for trend tests were 0.0195 and 0.0345, respectively). Further, in haplotype analyses, the male patients carrying the GA haplotype had a higher risk of GO (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.09-3.73) than those not carrying the GA haplotype. CONCLUSION: The present data suggest that TLR-9 gene polymorphisms were significantly associated with increased susceptibility of ophthalmopathy in male GD patients.

Association of interleukin-1beta (IL1B) polymorphisms with Graves' ophthalmopathy in Taiwan Chinese patients.

PURPOSE: To evaluate whether variations in the IL1B gene could be associated with Graves' ophthalmopathy (GO) in patients with Graves' disease (GD). METHOD: This case-control study included 471 Taiwan Chinese patients with GD (200 with GO and 271 without GO) and 160 healthy volunteers. Eight single-nucleotide polymorphisms (SNPs) in IL1B were genotyped with an allele-specific extension and ligation assay. RESULTS: In the IL1B SNPs examined, the C allele of rs1143634 was associated with GD, whereas the T/T genotype of the SNPs rs1143634 and rs16944 were less associated with the disease. The A/A genotype of the SNPs rs3917368 and rs1143643, which had the strongest interaction, may increase the risk of GO (P = 0.024 and P = 0.017, respectively). Several GD susceptibility and insusceptibility IL1B haplotypes have been identified, and the Ht4-GCGCCTCC haplotype, composed of eight SNPs and associated with low circulating IL1ß levels, may be protective against the development of GO (P = 0.025). Moreover, that the GO-susceptible genotype was associated with lower plasma IL1ß concentrations implies that the origin of GO may go beyond the IL1B polymorphism-associated elevation of circulating IL1ß. CONCLUSIONS: The data for IL1B polymorphisms and the association of GD and GO with plasma IL1ß levels show that IL1B polymorphisms may be associated with the development of GD and GO.

Secondary hypertension due to a renin-secreting juxtaglomerular cell tumor.

A juxtaglomerular cell tumor (JCT) is a rare, renin-secreting tumor of the kidney and can cause hypertension. JCT is pathologically benign, and resection of the tumor is curative for hypertension. We report the case of a 17-year-old girl who had hypertension and hypokalemia for 1 year. Laboratory studies showed increased basal plasma renin activity, but normal serum aldosterone level. Abdominal computed tomography disclosed a 2 cm solid mass in the left kidney. However, renal vein sampling and captopril test results were equivocal. Partial nephrectomy was performed and histologic examination demonstrated typical features of JCT. Hypertension and hypokalemia completely resolved postoperatively. JCT should be considered when investigating hypertensive individuals with high plasma renin activity.

Disease association of the CD103 polymorphisms in Taiwan Chinese Graves' ophthalmopathy patients.

OBJECTIVE: To evaluate whether variations in the CD103 gene could be associated with Graves' ophthalmopathy (GO) in patients with Graves' disease. DESIGN: Case-control study. PARTICIPANTS: A total of 484 Chinese patients with Graves' disease in Taiwan, including 203 patients with GO and 281 patients without GO, were enrolled. METHODS: Five single nucleotide polymorphisms (SNPs) in CD103 were genotyped using an assay-on-demand allelic discrimination assay and detection system according to the manufacturer's instructions. MAIN OUTCOME MEASURES: Association of SNPs in CD103 with the development of GO. RESULTS: The CD103 SNP rs11652878 was associated with GO, which may decrease the risk of GO by 1.57-fold (P = 0.029). The Ht5-GCGCG haplotype, composed of 5 SNPs in the CD103 gene (rs1716, rs3744679, rs11652878, rs16953477, and rs9905739), were protective haplotypes (P = 0.010). Moreover, the heterozygous genotype (Ht5/non-Ht5) was correlated with a reduced risk of GO and high grades of goiter as compared with the non-Ht5/non-Ht5 genotype (P = 0.006 and P = 0.048, respectively). Logistic analysis confirmed the contribution of CD103 rs11652878 to the protection of GO. CONCLUSIONS: These data suggest that patients with Graves' disease in the presence of the G allele of SNP rs11652878, especially Ht5-GCGCG, in CD103 are less susceptible toward the development of GO.

A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

Levels of retinol-binding protein 4 and uric acid in patients with type 2 diabetes mellitus.

Retinol-binding protein 4 (RBP4) is a novel adipocytokine. It was observed that retinoid intoxication was related to acute attacks of gout. Furthermore, animal study has shown that colchicine inhibits RBP secretion. The aim of this study was to explore the association between RBP4 level and metabolic parameters especially uric acid in patients with type 2 diabetes mellitus. Serum RBP4 level was measured by a commercial competitive enzyme-linked immunosorbent assay kit, and its correlation with clinical and metabolic parameters was analyzed. Data on 885 subjects were used in the analysis. Pearson correlations revealed that serum RBP4 level correlated positively with age, waist circumference, waist-to-hip ratio, systolic blood pressure, total cholesterol, triglyceride, uric acid, creatinine, and urine albumin-to-creatinine ratio. Serum RBP4 level correlated negatively with estimated glomerular filtration rate but did not correlate with body mass index, homeostasis model assessment, A(1C), or high-sensitivity C-reactive protein. Multiple linear regression analysis with serum RBP4 level as the dependent variable revealed that total cholesterol, triglyceride, uric acid, and albumin-to-creatinine ratio correlated independently and positively with serum RBP4 level and that estimated glomerular filtration rate correlated independently and negatively with serum RBP4 level. In conclusion, RBP4 level was independently associated with uric acid level.

p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases.

p53 protein participates in the processes of apoptosis, which is involved in a number of immunological reactions. In order to test whether the p53 gene could be used as a genetic marker for the prediction of the development of autoimmune thyroid diseases (AITD), we screened, by using polymerase chain reaction (PCR) analysis, for the C (CCC)/G (CGC) polymorphism at the p53 codon 72 (Pro 72/Arg 72) to determine the genotypes of 107 Hashimoto's thyroiditis (HT) and 90 Graves' disease (GD) patients, and 105 normal controls. The data demonstrated that, for the genotype analysis, HT patients featured an enhanced numerical ratio for the Arg/Arg homozygous genotype (33.7%) and a diminished ratio for the Arg/Pro heterozygous genotype (41.1%) at the p53 codon 72 than was the case for normal controls (Arg/Arg: 17.1% and Arg/Pro: 61.9%; P=0.005). The odds ratio for the risk of the Arg/Arg genotype's appearance, compared with that of the Arg/Pro and Pro/Pro genotypes combined, for the HT patient group was 2.450 (95% confidence interval: 1.274-4.716). With respect to allelic analysis, we did not observe significant difference in the frequency of appearance of the Arg allelic variant and the Pro allelic variant for the p53 codon 72 when comparing the HT patient group with the control group (P=0.208). On the other hand, GD patients presented no significant difference in distribution for both genotype and allelic frequencies (P=0.344 and 0.245, respectively) when compared with normal controls. In conclusion, HT patients feature a greater ratio of arginine homozygosity at p53 codon 72 than in the case for normal subjects. The p53 codon 72 proline/arginine polymorphism may be a genetic marker to predict the increased susceptibility of development of HT.

Lack of association between interleukin-4 gene polymorphisms and autoimmune thyroid diseases amongst Taiwanese Chinese.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are both common autoimmune diseases of the thyroid gland (AITD). The IL-4 is involved in both humoral and cellular immunity. The aim of this study was to test whether the IL-4 gene could be used as a genetic marker to predict the development of AITD amongst the Chinese population of Taiwan. For this study, a normal control group of 105 healthy subjects and two experimental groups featuring individuals afflicted with either GD (104 patients) or HT (109 patients) were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) polymorphism for the IL-4 gene intron 3 and PCR-based restriction analysis using endonuclease BsmFI was undertaken for the same gene at the promoter -590 position. We found no significant difference in the frequencies of presence of genotype and allelic variants for the IL-4 gene at both the intron 3 and the promoter regions between the normal control group and each of the two patient groups. These findings suggest that the IL-4 gene polymorphisms that arise at either intron 3 or promoter -590 positions are not suitable genetic markers for AITD among Taiwanese Chinese.

Association between vitamin-D receptor gene FokI polymorphism and Graves' disease among Taiwanese Chinese.

1,25(OH)(2)D(3), exerting its biological effects through the vitamin-D receptor (VDR), plays a role in the modulation of the human immune system. The aim of this study was to test for the presence of an association between VDR gene polymorphism and the susceptibility to Graves' disease (GD) for Taiwanese Chinese. Using a polymerase chain reaction (PCR)-based restriction analysis, we screened the VDR exon 2 start codon T/C (VDR-FokI) polymorphism to determine the genotypes for 88 GD patients and 90 normal controls. From the genotype analysis, GD patients featured a greater proportion of the CC genotype (44.3%) and a smaller proportion of the TT genotype (12.5%) than was the case for normal controls (CC: 23.3% and TT: 28.9%; chi-squared test, P=0.003). The odds ratios (ORs) for the risk of the CC genotype's appearance compared with the corresponding values for the TT and TC genotypes, for the GD patient group, were, 4.39 (95% confidence interval [CI]: 1.82-10.61) and 2.10 (95% CI: 1.06-4.18), respectively. With respect to the allelic analysis, we observed significantly increased C-allele (65.9%) and decreased T-allele (34.1%) frequencies among GD patients compared to normal controls (C: 47.2% and T: 52.8%; chi-squared test, P=0.002). The OR for the risk of appearance of the C allele in the GD-patient group was 1.93 (95% CI: 1.27-2.95). In conclusion, the VDR-FokI T/C polymorphism might be able to be used as a genetic marker to predict the likelihood of GD development.

Proinflammatory cytokine gene polymorphisms among Hashimoto's thyroiditis patients.

Proinflammatory cytokines are involved in the pathogenesis of Hashimoto's thyroiditis (HT). To test whether certain specific proinflammatory cytokine gene polymorphisms could be genetic markers for an individual's susceptibility to HT, we investigated single-site polymorphisms of certain proinflammatory cytokine genes of interest for 107 HT sufferers and 163 controls, subsequent to preparing the necessary experimental genomic DNA from peripheral blood, using a polymerase chain reaction (PCR)-based restriction analysis. The polymorphisms we detected were as follows: 1) C/T and E1/E2 polymorphisms for the interleukin (IL)-1beta gene at promoter (-511) and exon 5, respectively; 2) a variable number of tandem repeats (VNTRs) for the IL-1 receptor antagonist (IL-1Ra) gene at intron 2; 3) a C/G polymorphism for the IL-6 gene at promoter (-572); and 4) an A/G polymorphism for the tumor necrosis factor (TNF)-alpha gene at promoter (-308). The data demonstrated an increased ratio of CG genotype and decreased ratios of CC and GG genotypes (chi-squared test; P = 0.025) for the IL-6 gene promoter for HT patients when compared with normal controls. The odds ratio (OR) for the CG genotype, as compared to the GG genotype, for HT patients was shown to be 4.065 (95% confidence interval (CI): 1.268-13.032). Comparison of the genotype analysis for the remaining gene polymorphisms and the allelic analysis for all of the screened gene polymorphisms, however, all revealed no statistically significant difference between the two study groups as regards frequency of genotype. In conclusion, we suggest that an IL-6 gene promoter (-572) C/G polymorphism could represent a potential "candidate" genetic marker to predict an individual's susceptibility to HT.

Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto's thyroiditis in Chinese patients in Taiwan.

The etiology of the autoimmune thyroid, Hashimoto's thyroiditis (HT) is not very clear. However, genetic susceptibility is thought to play a critical role. The vitamin D receptor (VDR)-related endocrine system has been demonstrated to be able to carry out modulation of the immune response. Here, we investigated whether single nucleotide polymorphisms (SNPs) of VDR are associated with HT patients. VDR SNP was detected by polymerase chain reaction (PCR)-based restriction analysis in 109 patients with HT and 90 normal controls. Significant differences were found in the genotype distribution of VDR SNP between Hashimoto's thyroiditis patients and controls (P=0.0458). Allelic frequency of the VDR gene distinguished HT patients from controls (P=0.0089). The results revealed a significant difference between HT patients and normal controls in VDR SNP and a statistic correlation between VDR-FokI polymorphisms and HT formation. It could be concluded that patients who carry the C/C homozygote of the VDR-FokI gene polymorphism in exon 2 may have a higher risk of developing HT in Chinese patients in Taiwan.

Association between the TAP2 gene codon 665 polymorphism and Graves' disease.

A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303-10.598 and 1.020-4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449-3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development.

TAP 2 gene Msp-I polymorphism might be associated with calcium oxalate stone disease.

INTRODUCTION: Inflammation might be one of the causes of stone disease. The function of the transporter associated with antigen-processing protein (TAP) is related to immune response and inflammation. Our aim was to investigate the relationship between stone disease and 5 polymorphic sites of the TAP gene (TAP1-1, 1-2, 2-1, 2-2, 2-3). MATERIALS AND METHODS: We compared the frequencies of 5 polymorphisms in the TAP gene between 208 patients with recurrent calcium oxalate stone and 210 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis. RESULTS: Significant differences in the frequency of the polymorphism at the TAP2-2 site were detected between normal individuals and calcium stone disease patients (p<0.0001). The distribution of the genotype AA homozygote was higher in stone patients (33.3%) than in the control group (16.3%). The odds ratio for the A allele compared with the G allele was 2.097 (95% CI 1.571-2.802). CONCLUSIONS: We conclude that the TAP2-2 MspI polymorphism might be associated with calcium stone disease.

Glutathione S-transferase M1 gene but not insulin-like growth factor-2 gene or epidermal growth factor gene is associated with prostate cancer.

Prostate cancer is the most common urologic malignancy involving multiple factors. There is evidence that suggests that detoxification enzymes and growth factors may play a role in the formation of prostate cancer. Our aim was to investigate whether polymorphisms of glutathione S-transferase M1 (GST M1), insulin-like growth factor-2 (IGF-2), and epidermal growth factor (EGFR) genes could be used as genetic markers for risk of prostate cancer. In this study, we compared the frequency of the polymorphisms of GST M1, IGF-2, and EGFR genes among 96 patients with prostate cancer and 121 healthy male volunteers from the same geographic area (age, older than 60 years). There was significant difference in the GST M1 genotype between the prostate cancer group and the control group (P=0.042). The GST M1 null genotype was significantly higher in the cancer group (59.4%) than in the control group (45.5%). However, our study did not reveal a significant association between prostate cancer and the distribution of the IGF-2 or EGFR genotypes. This study suggests that the GST M1 gene, but not the IGF-2 or the EGFR genes, may be a risk factor of developing prostate cancer in Taiwan.