Associations between SLC2A9 polymorphisms and gout susceptibility : A meta-analysis.

OBJECTIVE: The aim of this study was to determine whether polymorphisms in solute carrier family 2 and facilitated glucose transporter member 9 (SLC2A9) are associated with susceptibility to gout. METHODS: A meta-analysis was conducted on associations between the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 and gout susceptibility using fixed and random effects models. RESULTS: Eleven comparative studies comprising 1,472 patients and 3,269 controls from Caucasian and Asian populations were included in this meta-analysis. The meta-analysis identified a significant negative association between gout and allele 2 (minor) of the rs12510549 polymorphism in the overall population (OR = 0.641, 95 % CI = 0.540-0.761, P = 4.1 × 10-7). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.647, 95 % CI = 0.542-0.771, P = 1.2 × 10-6) but not in Asians (OR = 0.515, 95 % CI = 0.214-1.236, P = 0.137). The meta-analysis showed a significant negative association between gout and allele 2 of the rs16890979 polymorphism in all study subjects (OR = 0.229, 95 % CI = 0.084-0.628, P = 0.004). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.469, 95 % CI = 0.317-0.695, P = 1.6 × 10-6) and in Asians (OR = 0.192, 95 % CI = 0.072-0.513, P = 0.001). A significant negative association was found between allele 2 of the rs1014290 polymorphism and gout susceptibility in Asians (OR = 0.597, 95 % CI = 0.478-0.746, P = 5.4 × 10-6) but not in Caucasians (OR = 0.778, 95 % CI = 0.595-1.043, P = 0.095). CONCLUSIONS: This meta-analysis shows that the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 protect against the development of gout in Caucasians and/or Asians.

Association between shortened telomere length and systemic lupus erythematosus: a meta-analysis.

Objective We aimed to evaluate the relationship between telomere length and systemic lupus erythematosus (SLE). Methods PUBMED and EMBASE databases were searched; meta-analyses were performed comparing telomere length in SLE patients and healthy controls, and on SLE patients in subgroups based on ethnicity, sample type, assay method and data type. Results Eight studies including 472 SLE patients and 365 controls were ultimately selected which showed that telomere length was significantly shorter in the SLE group than in the control group (standardized mean difference (SMD) = -0.835, 95% confidence interval (CI) = -1.291 to -0.380, p = 3.3 × 10-4). Stratification by ethnicity showed significantly shortened telomere length in the SLE group in Caucasian, Asian and mixed populations (SMD = -0.455, 95% CI = -0.763 to -0.147, p = 0.004; SMD = -0.887, 95% CI = -1.261 to -0.513, p = 3.4 × 10-4; SMD = -0.535, 95% CI = -0.923 to -0.147, p = 0.007; respectively). Furthermore, telomere length was significantly shorter in the SLE group than in the control group in whole blood and peripheral blood mononuclear cell groups (SMD = -0.361, 95% CI = -0.553 to -0.169, p = 2.3 × 10-4; SMD = -1.546, 95% CI = -2.583 to -0.510, p = 0.003; respectively); a similar trend was observed in leukocyte groups (SMD = -0.699, 95% CI = -1.511 to -0.114, p = 0.092). Meta-analyses based on assay method or data type revealed similar associations. Conclusions Our meta-analysis demonstrated that telomere length was significantly shorter in patients with SLE, regardless of ethnicity, sample type or assay method evaluated.

The association between susceptibility to inflammatory arthritis and miR-146a, miR-499 and IRAK1 polymorphisms. A meta-analysis.

OBJECTIVE: The aim of this study was to explore whether polymorphisms in miR-146a, miR-499 and IRAK1 are associated with susceptibility to inflammatory arthritis. METHODS: Manual searches performed in the MEDLINE and EMBASE databases were used to identify published articles in which the roles of microRNA (miRNA) and IRAK1 polymorphisms in inflammatory arthritis were determined. A meta-analysis was conducted to investigate associations of the miR-146a rs2910164, miR-499 rs3746444, IRAK1 rs3027898 and IRAK1 rs1059703 polymorphisms with susceptibility to inflammatory arthritis. RESULTS: Nine studies containing 1224 patients and 1841 controls were included in the meta-analysis. The meta-analysis revealed no association between inflammatory arthritis and the rs2910164 C allele of miR-146a (odds ratio, OR = 0.974; 95 % confidence interval, CI = 0.810-1.091; p = 0.650). Stratification by ethnicity or disease type revealed no association between the miR-146a C allele and inflammatory arthritis in European, Middle Eastern or Asian patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA). However, the meta-analysis revealed an overall association between RA and the miR-499 rs374644 C (OR = 1.123, 95 % CI = 1.019-2.586, p = 0.041); stratification by ethnicity revealed a particular association in Middle Eastern populations (OR = 1.943, 95 % CI = 1.508-2.504, p = 2.7 × 10(-8)). The meta-analysis of IRAK1 polymorphisms revealed an association between inflammatory arthritis and the rs3027898 CC genotype (OR = 2.602, 95 % CI = 1.387-4.879, p = 0.003). An analysis using the homozygote contrast showed the same pattern for the rs3027898 CC genotype (OR = 2.472, 95 % CI = 1.300-4.700, p = 0.006). No association between inflammatory arthritis and the rs1059703 polymorphism was found. CONCLUSION: This meta-analysis suggests that the miR-499 rs374644 and IRAKI rs3027898 polymorphisms are associated with susceptibility to inflammatory arthritis.

Meta-analysis of SLC22A4 and RUNX1 polymorphisms : Associations with rheumatoid arthritis susceptibility.

OBJECTIVE: The aim in this study was to determine whether solute carrier family 22, member 4 (SLC22A4), and runt-related transcription factor 1 (RUNX1) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) in populations of different ethnicities. METHODS: We conducted a literature search using the MEDLINE and EMBASE, and performed a meta-analysis using a fixed or random effects model. RESULTS: A total of 26 comparative studies from 14 articles met the study inclusion criteria. Studies on the SLC22A4 polymorphism involved 12,458 RA patients and 9283 controls, and studies on the RUNX1 polymorphism involved 3958 RA patients and 3773 controls. The meta-analysis showed no association between the 22 + 21 genotype of the SLC22A4 F1 and RA in overall group [odds ratio (OR) 1.074, 95 % confidence interval (CI) 0.952-1.212, p = 0.245]. After stratification by ethnicity, the meta-analysis indicated that the 22 + 21 genotype of the SLC22A4 F1 was associated significantly with RA in the East Asian population, but not in the European population (OR 1.124, 95 % CI 1.018-1.240, p = 0.021; OR 0.981, 95 % CI 0.773-1.243, p = 0.871). CONCLUSION: This meta-analysis demonstrates that the SLC22A4 F1 polymorphism is associated with susceptibility to RA in East Asians, but not in Europeans.

Meta-analysis of functional MBL polymorphisms. Associations with rheumatoid arthritis and primary Sjögren's syndrome.

OBJECTIVE: The aim of this study was to determine whether functional mannose-binding lectin gene (MBL) polymorphisms are associated with the susceptibility to rheumatoid arthritis (RA) or primary Sjögren's syndrome (pSS). METHODS: A meta-analysis was conducted to investigate the potential association of RA or pSS with MBL polymorphisms, including the codon 54 (allele B), codon 57 (allele C), and codon 52 (allele D) variants of exon 1, and the - 550 (allele L) and - 221 (allele X) promoter variants. RESULTS: A total of 12 comparative studies, including eight RA (1623 patients and 1671 controls) and four pSS (280 patients and 516 controls) studies, were included in the meta-analysis. The meta-analysis revealed no association between the MBL B allele and RA in the overall study population (odds ratio [OR] 0.991, 95 % confidence interval [CI] 0.726-1.355, p = 0.957). However, the meta-analysis showed significant associations between the MBL D, H, and X alleles and RA in the overall population (OR 1.708, 95 % CI 1.077-2.707, p = 0.023; OR 1.936, 95 % CI 1.218-3.078, p = 0.005; OR 1.582, 95 % CI 1.216-2.057, p = 0.001, respectively). An association was found between the MBL B allele and pSS in the overall study population (OR 0.691, 95 % CI 0.541-0.917, p = 0.010). Stratification by ethnicity indicated a trend toward an association between the B allele and pSS in European populations, but no association in Asian populations (OR 0.689, 95 % CI 0.465-1.021, p = 0.063; OR 0.896, 95 % CI 0.311-2.562, p = 0.838, respectively). CONCLUSION: This meta-analysis demonstrated an association between the MBL D, L, and X alleles and the risk of RA. It also demonstrated an association between the MBL B allele and the susceptibility to pSS, suggesting a protective role of the MBL B allele against the development of pSS.

Uterine angiomyolipoma with metastasis in a woman with tuberous sclerosis: a case report.

Extrarenal angiomyolipomas (AMLs) have been reported at various anatomical sites such as the liver, spleen, abdominal wall, retroperitoneum, oral cavity, penis, spermatic cord, skin, and lung but are infrequently described in gynecological regions. However, only a few cases of extrarenal AML in the uterus have been reported. The authors describe a case of uterine AML in a 41-year-old woman with evidence of tuberous sclerosis. Initial diagnosis concluded with myoma based on the interpretation of imaging and other pathological parameters. However, after successful laparoscopic surgical staging, AML was diagnosed. To date, the feasibility of laparoscopic surgical diagnosis and the risks associated with this technique have not been reported. The authors briefly review the implementation of laparoscopic surgical staging to diagnose uterine AML.

Fabrication of hemispherical nano structure on a curved Al surface using low-temperature and high-voltage anodizing method.

A simple method of fabricating hemispherical nanostructures on a curved aluminum rod surface was presented. In conventional methods of fabricating nanopatterns on a curved aluminum surface, mechanical or chemical processes have been widely used for the lens technologies. Such processes are not only expensive with long processing times, however, but they also involve local fabrication and are limited in the dimension size. In this paper, a method of fabricating hemispherical nanostructures on a curved aluminum surface is suggested for a functional three-dimensional (3D) master using a low-temperature and high-voltage (LTHV) anodizing method. By reducing the aluminum reaction rate under a low-temperature environment, the reaction current density can be remarkably reduced even though a high voltage was induced. Using the LTHV anodizing method, the hemispherical pattern size can be easily controlled with respect to voltage variations. The sizes of the hemispherical nanopatterns were about 150-300 nm. Using the LTHV anodizing process, hemispherical nanostructures can be obtained on a curved aluminum surface with controllable pattern sizes of 150-300 nm without defects such as burring from Joule's heat, micro-scratches, and cracks. A curved 3D hemispherical nanostructure may be used as a master in the roll-to-roll process.

Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients.

BACKGROUND AND OBJECTIVE: Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the CYP3A5*3 genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the CYP3A5*3 genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients. METHOD: The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their CYP3A5 genotype was determined. Fourteen patients were CYP3A5 expressors (two for CYP3A5*1/*1 and 12 for CYP3A5*1/*3) and 21 patients were CYP3A5 non-expressors (CYP3A5*3/*3). Dose-normalized concentrations (mean +/- SD) of CBZ were 9.9 +/- 3.4 ng/mL/mg for CYP3A5 expressors and 13.1 +/- 4.5 ng/mL/mg for CYP3A5 non-expressors (P = 0.032). The oral clearance of CBZ was significantly higher in CYP3A5 non-expressors than that of CYP3A5 expressors (0.056 +/-0.017 L/h/kg vs. 0.040 +/- 0.014 L/h/kg, P = 0.004). The CYP3A5 genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.

Evaluation of serotyping using monoclonal antibodies and PCR-RFLP for Chlamydia trachomatis serotype identification.

We compared genotyping by restriction fragment length polymorphism (RFLP) analysis of the amplified omp1 gene with serotyping by dot enzyme-linked immunosorbent assay (dot-ELISA) to determine the suitability of RFLP analysis for epidemiologic study. Fifteen prototypes of Chlamydia trachomatis and 30 clinical isolates were used in this study. To serotype with dot-ELISA, chlamydia antigen was spotted onto a series of replicate nitrocellulose membrane patches and reacted with 11 mAbs that distinguish the 15 known serovars of C. trachomatis. For RFLP analysis, the amplified chlamydia omp1 gene was digested with AluI to differentiate serovars A to K and L1 to L3. Serovars of C, H, I, J, and L3 were further typed by RFLP analysis after digestion with HinfI, and a combination of EcoRI and DdeI. PCR-based RFLP could identify serotype of 28 among 30 clinical isolates tested. The remaining two untypical isolates were probably due to double infections or mechanical transferring error. Serotyping of C. trachomatis isolates shows that serovars E, D, F, and H are the most prevalent types found in urogenital samples in Korea. In this study, we show that RFLP analysis of amplified omp1 gene may be useful in genotyping C. trachomatis isolates.

Expression of tissue inhibitors of metalloproteinases (TIMPs) in hepatocellular carcinoma.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the remodelling of extracellular matrix (ECM), including basement membrane. ECM remodelling is associated with pathological processes, including hepatic fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the present study, we examined the expression of TIMP-1 and TIMP-2 in surgical specimen pairs of hepatocellular carcinoma and nontumoral liver and the correlation between their expression and clinicopathological characteristics. METHODS: The localization of both transcripts and protein of TIMP-1 and TIMP-2 was studied by using in situ hybridization and immunohistochemistry. RESULTS: TIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte, sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1 was stronger than that of TIMP-2. The results of immunohistochemical stainings were concordant with those obtained by in situ hybridization. Expression of TIMP-1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the portions of the tumors adjacent to the capsules. However, a clear difference in TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types. The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with variable clinicopathological characteristics. CONCLUSION: TIMPs was expressed in tumor cells and many cell types of the nontumoral liver. Further investigations for TIMPs' unknown functional role are needed.

Peptide vaccines incorporating a 'promiscuous' T-cell epitope bypass certain haplotype restricted immune responses and provide broad spectrum immunogenicity.

An ideal peptide vaccine should contain both B- and T-cell epitopes. Recognition of antigen by B cells is highly dependent on the three-dimensional conformation of the antigen whereas T cells recognize antigen only after it has been processed to release a peptide fragment which is bound to the major histocompatibility complex (MHC) class II molecule. However, T cells provide 'help' to B cells displaying the same processed, MHC-restricted form of the antigen, demonstrating that the T-cell response to a protein antigen is under genetic control. Thus, strategies for co-inclusion of T cell 'helper' epitopes with the B-cell determinant elicit immune responses that are in most cases genetically restricted to only one or a few alleles of the MHC with limited activity across divergent MHC class II haplotypes. This genetically restricted T cell stimulatory activity of peptides is a serious obstacle and consequently such constructs would be of limited practical value as a vaccine targeted to a majority of an outbred population. In the study described here, we have engineered two peptides to encompass the sequences from the universally immunogenic tetanus toxoid (TT) epitope and the contraceptive vaccine candidate lactate dehydrogenase C4 (LDH-C4). We demonstrate the feasibility of using 'promiscuous' T-cell epitopes colinearly constructed with a defined B-cell epitope to induce high titer antipeptide IgG antibodies specific for native protein antigen LDH-C4 in several inbred strains of mice, outbred mice and rabbits. There appears to be a strong correlation between the capacity for the hybrid peptides to be stimulatory for the corresponding T cells in C57BL/6 (H-2b) and C3H/HeJ (H-2k) mice and their ability to be immunogenic. This correlation, however, appears to break down in H-2d strains of mice since no antibodies were detected in BALB/c and barely detectable levels of antibodies in B10.D2 although activated T cells were detectable. Conversely, high titers of antipeptide antibodies are elicited in some strains (B10.BR (H-2k); C57BL/10 (H-2b) without detectable IL-2 responses. Finally, we show that a determinant which was previously restricted to H-2k can be rendered immunogenic in H-2b with the 'promiscuous' TT epitope. Thus, certain haplotype-restricted immune responses can be bypassed, setting forth the ground work for the design of a universal vaccine by broadening the effective response in a larger number of individuals typical of the genetically diverse outbred human population.