Vascular endothelial growth factor gene polymorphisms and psoriasis susceptibility: a meta-analysis.

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted to examine the associations between the +405 C/G, -460 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and psoriasis using allele contrast and recessive, dominant, and additive models. Seven studies on VEGF polymorphisms and psoriasis involving 1956 subjects (psoriasis patients 665, controls 1291) were included in this meta-analysis. We observed no association between psoriasis and the VEGF +405 C allele in all study subjects (odds ratio = 0.984, 95% confidence interval = 0.754-1.285, P = 0.906), but stratification by ethnicity indicated a significant association between the VEGF +405 C allele and psoriasis in Asians (odds ratio = 0.762, 95% confidence interval = 0.628-0.923, P = 0.005). In addition, we observed a significant association between the VEGF -460 C allele and psoriasis in Europeans (odds ratio = 0.807, 95% confidence interval = 0.672-0.968, P = 0.021). Meta-analyses of the -1154 A/G polymorphism also revealed a significant association with psoriasis in Europeans. However, the VEGF -2578 A/C polymorphism showed no association in all subjects or in Europeans or Asians. This meta-analysis suggests the VEGF +405 C/G polymorphism confers susceptibility to psoriasis in Asians, and that the -460 C/T and -1154 A/G polymorphisms confer susceptibility to psoriasis in Europeans.

Associations between tumor necrosis factor-α polymorphisms and susceptibility to pulmonary tuberculosis: meta-analysis.

The aim of this study was to determine whether tumor necrosis factor-α (TNF-α) polymorphisms are associated with susceptibility to pulmonary tuberculosis (PTB) in different ethnic populations. MEDLINE and Embase databases and manual searches were employed to identify articles in which TNF-α polymorphisms were determined in patients with PTB and controls. A meta-analysis was conducted on the associations of the TNF-α -308A/G, -238A/G, and -857T/C polymorphisms with PTB susceptibility. A total of 13 studies met the inclusion criteria, including 12, 6, and 4 studies on TNF-α -308A/G, -238A/G, and -857T/C polymorphisms, respectively. Meta-analysis showed no association between the TNF-α -308A allele and PTB susceptibility in all study subjects (odds ratio, OR = 1.182, 95%CI = 0.989-1.411, P = 0.066). After stratification by ethnicity, TNF-α -308A was not found to be associated with PTB in the European, Asian, or Middle East populations. No association was identified between PTB susceptibility and the TNF-α -238A allele in all study subjects (OR = 1.031, 95%CI = 0.741-1.436, P = 0.855), or in the European and Asian populations. However, TNF-α -857T was significantly associated with PTB susceptibility specifically in Asians (OR = 0.682, 95%CI = 0.550-0.846, P = 4.8 x 10(-5)). Meta-analysis using the dominant model, recessive model, or homozygote contrast showed the same pattern of results as for the TNF-α -857T allele. Overall, no correlation was noted between the TNF-α -308A/G and -238A/G polymorphisms and PTB susceptibility. However, the TNF-α -857T/C polymorphism was found to be associated with PTB susceptibility in the Asian population.

Vitamin D receptor gene FokI, TaqI, BsmI, and ApaI polymorphisms and susceptibility to pulmonary tuberculosis: a meta-analysis.

The aim of this study was to determine whether vitamin D receptor (VDR) genetic polymorphisms are associated with the susceptibility to pulmonary tuberculosis (PTB). MEDLINE and Embase databases and manual literature searches were used. A meta-analysis was conducted on the associations between the VDR FokI, TaqI, BsmI, and ApaI polymorphisms and PTB susceptibility. A total of 16 studies comprising 3231 patients and 3670 controls met the study inclusion criteria, consisting of 14 studies on the VDR FokI polymorphism, 13 on the VDR TaqI polymorphism, 8 on the VDR BsmI polymorphism, and 5 on the VDR ApaI polymorphism. Meta-analysis of the VDR FokI polymorphism showed no association between PTB and the f allele of the VDR FokI polymorphism (long variant) in all subjects (OR = 1.070, 95%CI = 0.979-1.169, P = 0.134). In contrast, after stratification by ethnicity, meta-analysis indicated that the VDR FokI F allele (short variant) was associated with PTB risk in an East Asian population (OR = 1.507, 95%CI = 1.192-1.906, P = 0.001). Meta-analysis revealed no association between PTB susceptibility and the VDR TaqI t allele in all study subjects (OR = 0.986, 95%CI = 0.839-1.159, P = 0.866) or in individual ethnic populations. Furthermore, a risk of PTB was not associated with the BsmI and ApaI polymorphisms. This meta-analysis suggested that the VDR FokI polymorphism is associated with a susceptibility to PTB in East Asians.

Estrogen receptor 1 PvuII and XbaI polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

The aim of this study was to explore whether estrogen receptor 1 (ESR1) PvuII and XbaI polymorphisms are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between AD and ESR1 PvuII and XbaI polymorphisms as well as haplotypes of the ESR1 PvuII and XbaI polymorphisms. A total of 1359 patients and 1387 controls from 9 studies on the ESR1 PvuII polymorphism and 1525 patients and 1575 controls from 8 studies on the ESR1 XbaI polymorphism were included in this meta-analysis. Gender-specific meta-analysis showed an association between the ESR1 PP+Pp genotype and AD in males (OR = 0.302, 95%CI = 0.100-0.914, P = 0.034), but not in females. No association was observed between AD and the ESR1 XbaI X allele (OR = 1.114, 95%CI = 0.868-1.429, P = 0.397). However, country-specific meta-analysis identified an association between AD and the ESR1 X allele in Japanese (OR = 1.386, 95%CI = 1.055-1.822, P = 0.019), but not Chinese or Italian populations. Meta-analyses results indicated an association between the PP/XX haplotypes and AD in Chinese population (OR for PP/XX vs others = 2.758, 95%CI = 1.750-4.346, P = 1.2 x 10(-6)). This meta-analysis showed associations between the ESR1 PvuII polymorphism and AD susceptibility in males, between AD risk and the ESR1 XbaI polymorphism in the Japanese population, and between the PP/XX haplotype and AD susceptibility in the Chinese population.

Meta-analysis of differentially expressed genes in ankylosing spondylitis.

The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in ankylosing spondylitis (AS). We performed a meta-analysis using the integrative meta-analysis of expression data program on publicly available microarray AS Gene Expression Omnibus (GEO) datasets. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using the Kyoto Encyclopedia of Genes and Genomes. Four GEO datasets, including 31 patients with AS and 39 controls, were available for the meta-analysis. We identified 65 genes across the studies that were consistently DE in patients with AS vs controls (23 upregulated and 42 downregulated). The upregulated gene with the largest effect size (ES; -1.2628, P = 0.020951) was integral membrane protein 2A (ITM2A), which is expressed by CD4+ T cells and plays a role in activation of T cells. The downregulated gene with the largest ES (1.2299, P = 0.040075) was mitochondrial ribosomal protein S11 (MRPS11). The most significant GO enrichment was in the respiratory electron transport chain category (P = 1.67 x 10-9). Therefore, our meta-analysis identified genes that were consistently DE as well as biological pathways associated with gene expression changes in AS.

Associations between TNF-α polymorphisms and susceptibility to rheumatoid arthritis and vitiligo: a meta-analysis.

We investigated whether the tumor necrosis factor-a (TNF-α) promoter -238 A/G and -308 A/G polymorphisms are associated with rheumatoid arthritis (RA) and vitiligo susceptibility. MEDLINE and EMBASE databases and a manual search were used to identify articles in which TNF-α polymorphisms were determined in RA or vitiligo patients and controls. Meta-analysis was used to examine the associations between the TNF-α -238 A/G polymorphism and RA and vitiligo using the allelic contrast and dominant models. Fifteen studies (10 RA and 5 vitiligo) involving 3678 cases and 4400 controls were considered. We observed an association between the TNF-α -238 A allele and RA when all subjects were considered [odds ratio (OR) = 0.686, 95% confidence interval (CI) = 0.476-0.968, P = 0.043]. After stratification by ethnicity, we found no association between the TNF-α -238 A allele and RA in European or Asian populations. We observed no association between the TNF-α -308 A allele and vitiligo (OR = 1.787, 95%CI = 0.894-3.573, P = 0.101). However, the adjusted OR by the trim-and-fill technique was significant (OR = 2.064, 95%CI = 1.138- 3.743). After stratification by geographic continent, the TNF-α -308 A allele was significantly associated with vitiligo in Middle Eastern populations (OR = 1.569, 95%CI = 1.224-2.013, P = 3.8 x 10(-5)). The TNF-α -238 A/G polymorphism was associated with RA susceptibility, and the TNF-α -308 A/G polymorphism may be a significant risk factor for vitiligo in Middle Eastern populations.

Genome-wide pathway analysis in amyotrophic lateral sclerosis.

The aims of this study were to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of amyotrophic lateral sclerosis (ALS) and to generate SNP-to-gene-to-pathway hypotheses. An ALS genome-wide association study (GWAS) dataset that included 483,051 SNPs in 276 patients with ALS and 271 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 19 candidate SNPs, 8 genes, and 9 pathways, which provided 8 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was that rs9352 alters the role of chromatin assembly factor 1 subunit A in the context of the pathways of chromatin and nucleosome assembly (nominal P < 0.001, false discovery rate (FDR) ≤ 0.001, 0.018, respectively). The second strongest was rs1046329 → HILS1 → chromatin assembly (nominal P < 0.001, FDR = 0.018). The third was rs11100790 → SMARCA5 → chromatin and nucleosome assembly (nominal P < 0.001, FDR ≤ 0.001, 0.018, respectively). The application of ICSNPathway analysis to the ALS GWAS dataset resulted in the identification of candidate SNPs, pathways, and biological mechanisms that might contribute to ALS susceptibility.

PPARγ Pro12Ala and His447His polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

We investigated whether Pro12Ala (C→G) and His447His (C→T) polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARγ) gene are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between the PPARγ Pro12Ala and His447His polymorphisms and AD in subjects. The meta-analysis was performed according to the apolipoprotein E (APOE) ɛ4 allele status. A total of eight studies were considered in our meta-analysis, comprising 2948 patients with AD and 3753 controls. Meta-analysis showed no association between AD and the PPARγ Pro12Ala G allele in any of the study subjects [odds ratio (OR) = 1.013, 95% confidence interval (95%CI) = 0.906-1.132, P = 0.821] or in the European and Asian populations (OR = 0.997, 95%CI = 0.890-1.118, P = 0.965; OR = 1.409, 95%CI = 0.832-2.387, P = 0.202, respectively). We tested whether the APOE ɛ4 allele affects the association between the PPARγ Pro12Ala polymorphism and AD. Meta-analysis showed no association between AD and the PPARγ G allele in any of the study subjects with or without the APOE ɛ4 allele. Meta-analysis showed no association between AD and the PPARγ His447His T allele in the European population (OR for T allele = 0.912, 95%CI = 0.732-1.136, P = 0.409). This meta-analysis has shown that there is a lack of association between the PPARγ Pro12Ala and His447His polymorphisms and AD risk.

TNF-α -308 A/G and -238 A/G polymorphisms and susceptibility to glaucoma: a meta-analysis.

The purpose of this study was to examine whether tu-mor necrosis factor-α (TNF-α) -308 A/G and -238 A/G polymorphisms confer susceptibility to glaucoma. A meta-analysis was conducted ex-amining the association between TNF-α -308 A/G and -238 A/G poly-morphisms and glaucoma. A total of 13 studies on TNF-α -308 A/G and 238 A/G polymorphisms were included in this meta-analysis. The meta-analysis revealed no association between the TNF-α -308 A al-lele and glaucoma [odds ratio (OR) = 1.403, 95% confidence inter-val (CI) = 0.784-2.513, P = 0.254]. Subgroup analysis by disease type revealed no association between the TNF-α -308 A allele and glau-coma. The meta-analysis revealed no significant association between the TNF-α -238 A allele and glaucoma (OR = 1.120, 95%CI = 0.708-1.773, P = 0.628). This meta-analysis showed no association between the A alleles of the TNF-α -308 A/G or -238 A/G polymorphisms and glaucoma.

Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to systemic sclerosis: a meta-analysis.

The purpose of this study was to examine whether the insertion (I) or deletion (D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with susceptibility to systemic sclerosis (SSc). A meta-analysis examining the associations between the ACE I/D polymorphism and SSc was conducted in overall and European populations using 1) allelic contrast (D vs I); 2) recessive (DD vs ID + II); 3) dominant (DD + ID vs II); and 4) additive (DD vs ID vs II) models. A total of 7 studies consisting of 837 cases and 754 controls were available for meta-analysis. The meta-analysis revealed no association between the D allele and SSc in any study subjects [odds ratio (OR) = 0.956, 95% confidence interval (CI) = 0.733-1.246, P = 0.737]. Stratification by ethnicity indicated no association between the D allele of the ACE I/D polymorphism and SSc in Europeans (OR = 1.117, 95%CI = 0.776-1.607, P = 0.551). Meta-analysis using all other genetic models showed the same D allele pattern in the overall and European groups. This meta-analysis showed that the ACE I/D polymorphism was not associated with susceptibility to SSc in the study subjects and in Europeans.

Meta-analysis demonstrates association between TLR polymorphisms and rheumatoid arthritis.

We investigated whether Toll-like receptor (TLR) polymorphisms confer susceptibility to rheumatoid arthritis and whether they influence clinical characteristics of rheumatoid arthritis. Studies were considered relevant for our meta-analysis if at least two comparisons of an issue were available. Eleven studies with 2078 patients with rheumatoid arthritis and 2581 controls were included, encompassing European and Asian studies. Meta-analysis of three European studies showed no significant association between the TLR4 Asp299Gly (rs4986790) polymorphism and rheumatoid arthritis (odds ratio = 0.897, 95% confidence interval = 0.734-1.096, P = 0.289). One Turkish study showed a significant difference between TLR9 rs187084 allele frequencies and rheumatoid arthritis patients and controls, while another study revealed a significant association between rheumatoid factor and TLR8 rs5741883. A Korean study on the numbers of guanine-thymine [(GT)(n)] repeats in intron II of the TLR2 gene found a significantly higher S-allele frequency in rheumatoid arthritis patients than in controls (30.3 vs 23.0%). Overall findings for the meta-analysis including all the studies conclude that TLR polymorphism is associated with development and clinical characteristics of rheumatoid arthritis in Asian and Middle East populations.

Comparison of inflammatory microRNA expression in healthy and periodontitis tissues

MicroRNAs (miRNAs) are short RNA molecules that negatively regulate gene expression primarily by degrading target mRNA or inhibit the translation of protein product. Recently, many reports have shown the altered miRNA expression in various diseases. However, there are no reports on miRNA expression related to periodontitis. Thus, this study aimed to compare the miRNAs differentially expressed in healthy and chronic periodontitis tissues and to determine the miRNAs closely associated with chronic periodontitis. To find out the miRNAs differentially induced in healthy and chronic periodontitis tissues, miRNA microarray was carried out and the expression of miRNAs was confirmed by real-time PCR. According to miRNA microarray analyses, six miRNA genes, let-7a, let-7c, miR-130a, miR301a, miR-520d, and miR-548a, were up-regulated more than 8 fold compared to the healthy gingiva. The expression of twenty-two miRNAs was increased more than 4 fold. Among these miRNAs, eight miRNAs which are known to be closely related to inflammation were selected. Six of these miRNA genes, miR-181b, miR-19b, miR-23a, miR-30a, miR-let7a, and miR-301a, were amplified successfully and increased much more in periodontitis gingivae than in healthy ones. In summary, this study indicate that six miRNAs up-regulated in periodontitis gingiva may play a key role in chronic periodontitis

Comparison of inflammatory microRNA expression in healthy and periodontitis tissues

MicroRNAs (miRNAs) are short RNA molecules that negatively regulate gene expression primarily by degrading target mRNA or inhibit the translation of protein product. Recently, many reports have shown the altered miRNA expression in various diseases. However, there are no reports on miRNA expression related to periodontitis. Thus, this study aimed to compare the miRNAs differentially expressed in healthy and chronic periodontitis tissues and to determine the miRNAs closely associated with chronic periodontitis. To find out the miRNAs differentially induced in healthy and chronic periodontitis tissues, miRNA microarray was carried out and the expression of miRNAs was confirmed by real-time PCR. According to miRNA microarray analyses, six miRNA genes, let-7a, let-7c, miR-130a, miR301a, miR-520d, and miR-548a, were up-regulated more than 8 fold compared to the healthy gingiva. The expression of twenty-two miRNAs was increased more than 4 fold. Among these miRNAs, eight miRNAs which are known to be closely related to inflammation were selected. Six of these miRNA genes, miR-181b, miR-19b, miR-23a, miR-30a, miR-let7a, and miR-301a, were amplified successfully and increased much more in periodontitis gingivae than in healthy ones. In summary, this study indicate that six miRNAs up-regulated in periodontitis gingiva may play a key role in chronic periodontitis

Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis.

Programmed cell death 1 (PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416-6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488-3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024-1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans.

Food-processing approaches to altering allergenic potential of milk-based formula.

All the major cow milk proteins in their native states are potential allergens in infants with milk allergy. Heat treatment can reduce the antigenicity of whey proteins considerably, but it has virtually no effect on the antigenicity of casein. Infants allergic to milk still react to heat-denatured whey proteins. Therefore heat denaturation alone cannot produce a formula with low allergenicity. Enzyme hydrolysis reduces the antigenicity and allergenicity of protein. Partial hydrolysis produces hydrolysate consisting mainly of large peptides, whereas extensive hydrolysis produces hydrolysate containing a mixture of large and small peptides and free amino acids. Enzyme hydrolysis often produces bitter peptides and destroys the physical functionality of protein. When hydrolysate formula is made, casein or whey protein hydrolysate is ultrafiltered to remove large residual peptides. Certain amino acids are fortified to provide a balanced amino acid profile. The final formulation must comply with the recommendations of the Codex Alimentarius Commission (FAO/WHO) and the U.S. Infant Formula Act to provide adequate infant nutrition. Protein hydrolysate-based formula can be improved by further reducing the residual allergenicity, increasing the small peptide content, and improving the taste.