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Bladder cancer is one of the major cancer types and both environmental factors and genetic background play important roles in its pathology. Kaohsiung is a high industrialized city in Taiwan, and here we focused on this region to evaluate the genetic effects on bladder cancer. Muscarinic acetylcholine receptor M3 (CHRM3) was reported as a key receptor in different cancer types. CHRM3 is located at 1q42-43 which was reported to associate with bladder cancer. Our study attempted to delineate whether genetic variants of CHRM3 contribute to bladder cancer in Chinese Han population in south Taiwan. Five selected SNPs (rs2165870, rs10802789, rs685550, rs7520974, and rs3738435) were genotyped for 30 bladder cancer patients and 60 control individuals and genetic association studies were performed. Five haplotypes (GTTAT, ATTGT, GCTAC, ACTAC, and ACCAC) were found significantly associated with low CHRM3 mRNA level and contributed to increased susceptibility of bladder cancer in Kaohsiung city after rigid 10000 consecutive permutation tests. To our knowledge, this is the first genetic association study that reveals the genetic contribution of CHRM3 gene in bladder cancer etiology. [ABSTRACT FROM AUTHOR]

Patients demonstrate notable variations in disease progression following human immunodeficiency virus (HIV) infection. We aimed to identify ZNRD1 and RNF39 genetic variants linked to AIDS progression. We conducted a genetic association study in HIV-1-infected Han Chinese patients residing in Taiwan. The clinical characteristics of 143 HIV-1-infected patients were measured, and patients were split into 2 groups: AIDS progression and AIDS non-progression. Genotyping of ZNRD1 and RNF39 was performed in all participants. We found that patients in the AIDS progression group had higher HIV-1 viral loads and lower CD4 cell counts than did patients in the AIDS non-progression group. The frequency of the AA genotype of ZNRD1 (rs16896970) was lower in the AIDS progression group than in the AIDS non-progression group. Patients with AA genotypes had lower levels of HIV-1 viral loads and higher levels of CD4 cell counts than did patients with AG+GG genotypes. AIDS progression in patients with the AA group is significantly different from that in patients with the AG and GG groups by using Kaplan-Meier survival analysis. The hazard ratio for progression was lower in the AA group than in the AG and GG groups. We identified a SNP that contributes to AIDS progression in HIV-1-infected patients in this population. This SNP had a significant protective influence on AIDS progression, and polymorphisms of the ZNRD1 gene may play a role in the pathogenesis of HIV-1 infection. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous study indicated that DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two 8-oxoguanine glycosylase 1 ( OGG1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 384 Taiwanese individuals (192 patients with RA and 192 controls). Our data showed that statistically significant difference in genotype frequency distributions was found at rs3219008 SNP between patients with RA and control groups ( P = 5.6E-0.5). Our data also indicated that individuals with the AG genotype at rs3219008 SNP may have a higher risk of developing RA. We did not observe any statistically significant association of OGG1 haplotype frequencies (rs159153 and rs3219008) with RA progression. The study suggested that OGG1 polymorphisms (rs159153 and rs3219008) are associated with RA progression and that these may be used as molecular markers of RA. [ABSTRACT FROM AUTHOR]

Abstract: Background: The national hepatitis B (HB) vaccination program in Taiwan that began in 1984 has resulted in a significant reduction in the carrier rate among children. However, a significant proportion of Taiwanese neonatal HB immunization recipients have exhibited low anti-HBs titers that fall to non-protective or undetectable levels. Methods: We recruited 1677 entering freshman and graduate student participants at a Taiwanese university health center, grouped them into three age groups representing three stages of Taiwan''s HB vaccination program, then conducted hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) serological surveillances for each individual. Univariate and multivariate regression analyses of clinical characteristics and Interleukin-10 (IL-10) genetic variations were also conducted. Results: A trend toward a decreasing HBsAg carrier rate was observed over the starting dates of the vaccination program (11.7%, 1.6% and 1.7% for age groups 1, 2 and 3, respectively), but we also observed an increasing rate of non-protective anti-HBs titers (15%, 26% and 50.3% for cohorts 1–3, respectively). The percentage of students with non-protective anti-HBs titers increased from 23.1% for students born in 1984, to 25.2% for those born in 1985, to 39.4% for birth-year 1986 students, to 45.7% for birth-year 1987 students, and to 56.5% for birth-year 1988 students. The risk for low anti-HBs titers increased concurrently with increases in systolic blood pressure (BP), the IL-10 ATA/ACC haplotype, and the IL-10 ATA present haplotype. Risk for low anti-HBs titers decreased with concurrent decreases in glucose ante cibum (AC, before meals) and the IL-10 ACC/ACC haplotype. Conclusions: These results suggest that the genetic determinants may also contribute to variations in anti-HBs titers in immune responses to HB vaccination. [Copyright &y& Elsevier]

Kawasaki disease (KD) is pediatric systemic vasculitis with the classic complication of coronary artery aneurysm (CAA). It is the leading cause of acquired cardiovascular diseases in children. Some severe cases present with multi-organ involvement or neurological dysfunction. To identify the role of the glutamate receptor, ionotropic, N-methyl-d-aspartate 3A (GRIN3A) in KD, we investigated genetic variations in GRIN3A in a Taiwanese cohort of 262 KD patients (76 with and 186 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between clinical characteristics and GRIN3A genetic variations in KD. According to univariate regression analysis, CAA formation in KD was significantly associated with fever duration (p < 0.0001), first Intravenous immunoglobulin (IVIG) used (days after day one of fever) (p < 0.0001), and the GRIN3A (rs7849782) genetic variant (p < 0.001). KD patients with GG+GC genotype showed a lower rate of developing CAA (GG+GC genotype: odds ratio = 0.26; 95% CI = 0.14–0.46). Significant associations were identified between KD with CAA complication and the GRIN3A (rs7849782) genetic variant by using multivariate regression analysis. Specifically, significant correlations were observed between KD with CAA complications and the presence of GG+GC genotypes for the GRIN3A rs7849782 single-nucleotide polymorphism (full model: odds ratio = 0.25; 95% CI = 0.14–0.46). Our results suggest that a polymorphism of the GRIN3A gene may play a role in KD pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin-2 (IL-2), one of the crucial immunoregulatory cytokines required for T lymphocyte activation, plays an important role in autoimmune diseases. An IL-2 genetic G/T polymorphism (rs2069763) has been linked with multiple sclerosis and rheumatoid arthritis. We tested a hypothesis that this polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Han Chinese SLE patients and a healthy control group in Taiwan. Our results indicate (a) a significantly higher G allele frequency in SLE patients (P =1.91×10−14; OR=3.94; 95% CI=2.74–5.66), (b) a significantly higher G allele frequency in SLE patients with antinuclear antibodies (ANA) (P =0.033; OR=4.21; 95% CI=1.01–17.51) and (c) a significantly lower G allele frequency in SLE patients with discoid rash (P =0.019; OR=0.41; 95% CI=0.19–0.88). Our results suggest that this polymorphism may be involved in the genetic background of Taiwanese SLE. [Copyright &y& Elsevier]

Abstract: Studies of the human cytomegalovirus (HCMV) glycoprotein N (gpUL73-gN) showed that genotypic variations exist in different geographic areas, with gN-2 unidentified in Chinese population. The purpose of this study was to determine the HCMV gN variants in the Chinese population of Taiwan. Primers were designed and a polymerase chain reaction (PCR) was carried out on the UL73 gene. The PCR products were subjected to restriction fragment length polymorphism (RFLP) analysis. The same PCR-RFLP assay was repeated using primers published previously to demonstrate the influence of primer design. Of the 48 clinical HCMV isolates, 33 were positive for PCR products by both primer sets. Fifteen were positive only by the “in-house” PCR. The distribution of gN-1, gN-2, gN-3, and gN-4 by RFLP analysis was 14:11:7:17, with one isolate positive for both gN-1 and gN-2. The published primers detected the four genotypes with the number of 14:0:2:17. The under-representation of gN-2 and gN-3 by the method published previously may be due to inappropriate primer design when re-examining the sequences. On the basis of the results of this study, gN-2 is not the rarest gN genotype in the Chinese population of Taiwan. The design of primers used for PCR-RFLP genotyping may have a great influence on the frequency distribution of HCMV genomic variants. [Copyright &y& Elsevier]