MicroRNA-29: A Crucial Player in Fibrotic Disease.

Fibrosis is a common pathological state characterized by the excessive accumulation of extracellular matrix components, but the pathogenesis of the disease is still not clear. Previous studies have shown that microRNA-29 (miR-29) can play pivotal roles in the regulation of a variety of organ fibrosis, including cardiac fibrosis, hepatic fibrosis, lung fibrosis, systemic sclerosis, and keloid. In this review, we outline the structure, expression, and regulation of miR-29 as well as its role in fibrotic diseases.

From genetics to epigenetics: new insights into keloid scarring.

Keloid scarring is a dermal fibroproliferative response characterized by excessive and progressive deposition of collagen; aetiology and molecular pathology underlying keloid formation and progression remain unclear. Genetic predisposition is important in the pathogenic processes of keloid formation, however, environmental factors and epigenetic mechanisms may also play pivotal roles. Epigenetic modification is a recent area of investigation in understanding the molecular pathogenesis of keloid scarring and there is increasing evidence that epigenetic changes may play a role in induction and persistent activation of fibroblasts in keloid scars. Here we have reviewed three epigenetic mechanisms: DNA methylation, histone modification and the role of non-coding RNAs. We also review the evidence that these mechanisms may play a role in keloid formation - in future, it may be possible that epigenetic markers may be used instead of prognostic or diagnostic markers here. However, there is a significant amount of work required to increase our current understanding of the role of epigenetic modification in keloid disease.

Pivotal MicroRNAs in Melanoma: A Mini-Review.

Melanoma is a common skin cancer associated with ultraviolet light exposure and genetic variance. However, the etiology and molecular mechanisms of melanoma remain unknown. Recent studies have shown that microRNAs (miRNAs) can play key roles in the development and prognosis of this disease. In this study, we reviewed several pivotal miRNAs that may contribute to melanoma by involvement in the processes of invasion, migration, and metastasis of melanoma cells.

The null polymorphism of the GSTM1/T1 gene is not associated with susceptibility to systemic lupus erythematosus: a meta-analysis.

Previous studies have suggested that the null polymorphism of the glutathione S-transferases M1/T1 (GSTM1/T1) gene may be associated with the risk of developing systemic lupus erythematosus (SLE). We further explored this potential association using a meta-analysis. A systematic literature search was carried out in the scientific literature databases and we used odds ratios (OR) and 95 % confidence intervals (CIs) to evaluate the strength of this association. All statistical analyses were calculated using Stata software 11.0, and Bonferroni correction was used to adjust the p values. Nine eligible articles with 1,850 patients and 2,826 controls were identified. Our results showed the null polymorphism of the GSTM1 gene was associated with SLE in East Asians (OR 1.32, 95 % CI 1.04-1.69, p = 0.024), but not in Europeans and Africans. However, when Bonferroni corrections were applied (p = 0.05/2 = 0.025), we could not be sure of this association. We further analysed the associations between the GSTT1 gene null polymorphism and the risk of SLE. The results of this investigation showed that this null polymorphism was not associated with susceptibility to SLE in all included populations. In conclusion, the null polymorphism of GSTM1/T1 gene may not be associated with the risk of SLE. More studies are needed to confirm this lack of association between key oxidative defense genes and susceptibility to SLE in the future.

Val158Met polymorphism of COMT gene and Parkinson's disease risk in Asians.

In previous study, we have found the catechol-O-methyltransferase (COMT) Val158Met polymorphism as an associated risk factor for Parkinson's disease (PD) in Asian rather than Caucasian populations. The aim of this study was to further evaluate the associations of PD risk with COMT polymorphisms in different Asian populations. We carried out a retrieval of studies that investigated associations between COMT Val158Met polymorphism and PD risk in Asians, and included the study if it met the eligibility criteria. Stata version 12.0 was used to analyze the data. A total of 13 studies including 1,834 patients and 2,298 controls were included. The overall result indicated that COMT Val158Met polymorphism was significantly associated with the risk of PD in Asians (AA vs others: OR = 1.58, 95 % CI 1.26-1.97, p < 0.001; GG vs AA: OR = 0.63, 95 % CI 0.47-0.85, p = 0.002; AA vs GA: OR = 1.58, 95 % CI 1.24-2.00, p < 0.001). In Japanese population, the homozygote AA tends to increase the risk of PD (AA vs others: OR = 1.54, 95 % CI 1.10-2.15, p = 0.012; AA vs GA: OR = 1.61, 95 % CI 1.14-2.29, p = 0.008). This study showed that the Val158Met polymorphism of COMT gene may be associated with PD in Japanese rather than Chinese population. Further studies are needed to confirm this association in more ethnicities.

Association of COMT Val158Met polymorphism with wearing-off susceptibility in Parkinson's disease.

In previous study, we have found the catechol-O-methyltransferase (COMT) Val158Met polymorphism may be associated with the risk of Parkinson's disease (PD) in Asians, especially Japanese population. In this study, we further evaluated the associations of PD wearing-off susceptibility with COMT polymorphisms. We carried out a retrieval of studies and included the relevant studies which met the criteria. After the data were extracted, the Stata software 11.0 was used to analyse the genotype frequencies. A total of five studies were included. The pooled result indicated that genotype AA was significantly associated with the wearing-off risk of PD (AA vs. others: OR = 2.52, 95 % CI 1.21-5.26, P = 0.013; AA vs. GA: OR = 2.51, 95 % CI 1.18-5.34, P = 0.017; AA vs. GG: OR = 2.17, 95 % CI 1.09-4.33, P = 0.027). The results also showed allele A was correlated with PD wearing-off risk (A vs. G: OR = 1.95, 95 % CI 1.18-3.22, P = 0.009). In conclusion, this study suggested that Val158Met polymorphisms in COMT may increase the risk of wearing-off. Further studies with larger sample sizes are needed to confirm our results.

MicroRNA-499 rs3746444 polymorphism and autoimmune diseases risk: a meta-analysis.

BACKGROUND AND OBJECTIVE: MicroRNA (miR)-499 rs3746444 polymorphisms may participate in the pathogenesis of autoimmune diseases, but the results remain conflicting. We further investigated this association using a meta-analysis. METHODS: We conducted a retrieval of studies and obtained the eligible studies if they met inclusion criteria. Two researchers independently extracted the data from original articles. The genotype frequencies were analysed using Stata software. RESULTS: We finally archived six eligible studies that included 1,118 cases and 1,673 controls. After pooling the data, the results indicated that homozygote TT had an overall association with autoimmune diseases (TC + CC vs. TT: odds ratio [OR] 1.31, 95% CI 1.11-1.55, p = 0.001). The allele C, genotype TC and CC, may be associated with rheumatoid arthritis (RA) risks in Mediterranean populations (C vs. T: OR 2. 00, 95% CI 1.37-2.91, p < 0.001; TC vs. CC + TT: OR 1.76, 95% CI 1.27-2.44; p = 0.001; CC vs. TC + TT: OR 2.31, 95% CI 1.24-4.27, p = 0.008; CC vs. TT: OR 2.92, 95% CI 1.59-5.37, p = 0.001; TC vs. TT: OR 1.98, 95% CI 1.42-2.77). The genotype TT may decrease the risk of RA in Mediterranean populations (TC + CC vs. TT: OR 2.15, 95% CI 1.57-2.94, p < 0.001) rather than in East Asians. CONCLUSIONS: This study suggested that miR-499 polymorphisms were associated with a significantly increased risk of RA in Mediterranean populations.

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo.

BACKGROUND: Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo. AIMS: The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo. METHODS: We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0. RESULTS: Six case-control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR=1.59, 95% CI: 1.21-2.08, P=0.001; GSTT1: OR=1.30, 95% CI: 1.12-1.51, P=0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR=1.71, 95% CI: 1.12-2.63, P=0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR=1.76, 95% CI: 1.15-2.71, P=0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans. CONCLUSION: The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.

Apolipoprotein E gene polymorphism in psoriasis: a meta-analysis.

BACKGROUND AND AIMS: Several studies have shown that the apolipoprotein E (ApoE) gene is associated with the development of psoriasis. However, there is a controversy. The aim of the present study was to evaluate the association of psoriasis risk with ApoE polymorphisms. METHODS: We carried out a systematic search of studies that explored associations between ApoE polymorphisms and psoriasis. The genotype distribution of the control group in each study was calculated to determine whether or not there was compliance with the Hardy-Weinberg equilibrium. Overall effect sizes were assessed by odds ratio (OR) with 95% confidence intervals (CI). The selection to use the random-effects model or fixed-effects model depended on the size of the heterogeneity among the included studies. The fail-safe number (Nfs) was used to test the potential publication bias. We analyzed the data using Stata v.10.0. RESULTS: A total of seven studies with 966 patients and 1,086 controls were included. The results indicated that the ε2 allele was associated with increased risk of psoriasis (ε2 vs. ε3+ε4: OR = 1.47, 95% CI = 1.23-1.75, p <0.05), whereas the ε3 allele and ε3/ε3 genotype may decrease risk of psoriasis (OR = 0.71, 95% CI = 0.62-0.82, p <0.05; OR = 0.63, 95% CI = 0.52-0.77, p <0.05, respectively). In the subgroup analysis according to ethnicity, the increased risk of psoriasis remained in the Asian and European populations, whereas no significant association was found in other populations for other polymorphisms. CONCLUSIONS: Our study suggests that the ApoE polymorphisms are associated with the risk of psoriasis, especially ε2 and ε3 alleles. Further studies are needed to confirm our results.