METHODS: This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.
RESULTS: Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.
CONCLUSIONS: The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.
METHODS: Total 14 eligible articles published before March 2019 involving 35 studies, of which 21 studies (16,109 cases and 26,378 controls) for rs2205960 G > A, 8 studies (2,424 cases and 3,692 controls) for rs704840 T > G, and 6 studies (3,839 cases and 5,867 controls) for rs844648 G > A were included. Effects of the three respective polymorphisms on the susceptibility to ADs were estimated by pooling the odds ratios (ORs) with their corresponding 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous and homozygous models.
RESULTS: The overall analysis revealed that all the rs2205960 G > A, rs704840 T > G and rs844648 G > A polymorphisms could increase the risk of ADs in allelic, dominant, recessive, heterozygous and homozygous models. Furthermore, subgroup analysis showed that both rs2205960 G > A and rs704840 T > G were significantly associated with the susceptibility to systemic lupus erythematosus (SLE). What's more, statistically significant association between rs2205960 G > A polymorphism and primary Sjögren's syndrome (pSS) susceptibility was also observed in allelic, dominant and heterozygous models.
CONCLUSIONS: This current meta-analysis suggested that all of the three TNFSF4 polymorphisms may be associated with ADs susceptibility in Asians.
METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).
RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.
CONCLUSION: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.
METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.
RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.
CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.
RESULTS: A bulk segregant analysis (BSA) version of double-digest restriction-site associated DNA sequencing (BSA-ddRADseq) was developed and used to detect and position sex-linked single nucleotide polymorphism (SNP) markers in 19 families from the GIFT strain breeding nucleus and two Stirling families as controls (a single XY locus had been previously mapped to LG1 in the latter). About 1500 SNPs per family were detected across the genome. Phenotypic sex in Stirling families showed strong association with LG1, whereas only SNPs located in LG23 showed clear association with sex in the majority of the GIFT families. No other genomic regions linked to sex determination were apparent. This region was validated using a series of LG23-specific DNA markers (five SNPs with highest association to sex from this study, the LG23 sex-associated microsatellite UNH898 and ARO172, and the recently isolated amhy marker for individual fish (n = 284).
CONCLUSIONS: Perhaps surprisingly given its multiple origins, sex determination in the GIFT strain breeding nucleus was associated only with a locus in LG23. BSA-ddRADseq allowed cost-effective analysis of multiple families, strengthening this conclusion. This technique has potential to be applied to other complex traits. The sex-linked SNP markers identified will be useful for potential marker-assisted selection (MAS) to control sex-ratio in GIFT tilapia to suppress unwanted reproduction during growout.
RESULTS: Remarkably, modules could be grouped into just four functional themes: transcription regulation, immunological, extracellular, and neurological, with module generation frequently driven by lncRNA tissue specificity. Notably, three modules associated with the extracellular matrix represented potential networks of lncRNAs regulating key events in tumour progression. These included a tumour-specific signature of 33 lncRNAs that may play a role in inducing epithelial-mesenchymal transition through modulation of TGFβ signalling, and two stromal-specific modules comprising 26 lncRNAs linked to a tumour suppressive microenvironment and 12 lncRNAs related to cancer-associated fibroblasts. One member of the 12-lncRNA signature was experimentally supported by siRNA knockdown, which resulted in attenuated differentiation of quiescent fibroblasts to a cancer-associated phenotype.
CONCLUSIONS: Overall, the study provides a unique pan-cancer perspective on the lncRNA functional landscape, acting as a global source of novel hypotheses on lncRNA contribution to tumour progression.
DESIGN: Meta-analysis of odds ratios.
SETTING: Not applicable.
PATIENT(S): Subjects were women with RPL and their partners.
INTERVENTION(S): Not applicable.
MAIN OUTCOME MEASURE(S): The association between M2/ANXA5 haplotype and RPL was evaluated in a meta-analysis of odds ratios. We further scrutinized this association according to [1] the sequence of miscarriages, [2] the number of consecutive losses, [3] the extent of excluding other pathologies of RPL, and [4] the timing of fetal loss.
RESULT(S): Fourteen individual studies (n = 4,664 subjects) were included in this meta-analysis. The results show that women with the M2/ANXA5 haplotype have 1.54 times (95% confidence interval, 1.08-2.20) the odds of having associated RPL compared with women with the normal haplotype, regardless of consecutive or nonconsecutive pregnancy losses. Acknowledging the clinical heterogeneity among the studies, this significant association comes with a caveat that the lower bound of the confidence interval is close to unity. In couple populations (n = 2,449), M2/ANXA5 haplotype subjects have an odds ratio of 1.48 (95% confidence interval, 1.14-1.91) of experiencing RPL, which suggests contributions from paternal M2/ANXA5 carriers in RPL.
CONCLUSION(S): This meta-analysis ascertains that women with the M2/ANXA5 haplotype have a higher risk of experiencing RPL, especially consecutive early idiopathic RPL. Male partners with the M2/ANXA5 haplotype partly contribute to this risk. Hence, screening for the M2/ANXA5 haplotype as a panel of laboratory investigations for RPL is recommended.