Ping Shuai

Genetic associations of CLU rs9331888 polymorphism with Alzheimer’s disease: A meta-analysis

Recent studies showed the Clusterin gene (CLU) is associated with Alzheimers disease (AD). However, studies investigating the association of CLU single-nucleotide polymorphism (SNP) rs9331888 with AD are controversial. We then performed a meta-analysis to assess the association between CLU SNP rs9331888 and AD. Computerized bibliographic searches of PUBMED and AlzGene database were conducted for the period up to July, 2014. The strength of the association between SNP rs9331888 and AD was estimated by odds ratios (ORs) and OR 95% confidence intervals (CIs). A total of 11 studies composed of 8766 AD cases and 11,366 controls were included in this study. Significant association of SNP rs9331888 with AD was found in Caucasian population among allelic model (C vs. G: OR=1.12, 95%CI=1.06-1.17, P<0.001), additive model (CC vs. GG: OR=1.25, 95%CI=1.12-1.40, P<0.001), recessive model (CC vs. CG+GG: OR=1.20, 95%CI=1.07-1.34, P=0.001), and dominant model (CC+CG vs. GG: OR=1.13, 95%CI=1.06-1.21, P<0.001). No significant association among these models was found in Asian and overall populations. Sensitivity analysis found that one study caused the distinct heterogeneity in Asian subgroup. Our analysis demonstrated that CLU SNP rs9331888 might be associated with an increased AD risk in Caucasian population, but not in Asian population.

Association of SOD2 polymorphisms with primary open angle glaucoma in a Chinese population.

Abstract Background: Genetic factors have been studied extensively for their role in the pathogenesis of primary open angle glaucoma (POAG). This study was conducted to investigate whether manganese superoxide dismutase (SOD2) variants play a significant role in POAG in a Chinese population. Methods: This study included of 416 unrelated POAG patients and 997 unrelated control subjects. Four SOD2 tag single nucleotide polymorphisms (SNPs), including rs6917589 rs2842980, rs5746136 and rs4880, were genotyped by dye terminator-based SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. Results: Allelic association analysis showed that there were suggestive differences in the allelic distributions between POAG cases and controls for SNPs rs6917589 and rs5746136 (p = 0.0.046 and p = 0.032, respectively), but no statistically significant association was detected between the two SNPs and POAG after Bonferroni correction (p > 0.0125). The allele and genotype frequency in SNPs rs2842980 and rs4880 showed no statistically significant difference between POAG cases and controls (p = 0.128 and p = 0.867, respectively). SNP rs5746136 had a significant association with POAG in the recessive model (p = 0.003155). Haplotype ATGT generated from the four SNPs showed a trend of association with POAG (p = 0.0098). Conclusion: Our results showed a trend of association with POAG, suggesting that SOD2 may play a significant role in the development of POAG in the Chinese population. Further work with a larger sample size and functional study is needed to confirm the importance of the SOD2 gene in the pathogenesis of glaucoma.

Genetic associations in PLEKHA7 and COL11A1 with primary angle closure glaucoma: a meta-analysis.

Single nucleotide polymorphisms (SNPs) rs11024102 in PLEKHA7 and rs3753841 in COL11A1 were identified to be associated with primary angle closure glaucoma (PACG) by a recent large genome‐wide association study. This present study is to evaluate the association of PLEKHA7 rs11024102 and COL11A1 rs3753841 with PACG.

Associations of 6p21.3 Region with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD-associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 × 10−4 and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 × 10−4, OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders.

Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various cancers: a meta-analysis

Background Plasmacytoma variant translocation 1 (PVT1) has recently been reported to be aberrantly expressed and serves as a prognostic biomarker in many types of cancers. However, its prognostic significance remains controversial. Here, we conducted a meta-analysis to investigate the prognostic value of PVT1 expression in cancers. Results A total of 2109 patients from 20 studies were included. The results showed that elevated PVT1 expression predicted a poor outcome for overall survival (OS) in nine types of cancers (HR = 1.40, 95% CI: 1.21–1.59). Subgroup analysis indicated that there was a significant association between PVT1 overexpression and poor OS of patients with gastric cancer, gynecology cancer and lung cancer. Furthermore, we also found a negative significant relationship between PVT1 expression and disease-free survival (HR = 1.83, 95% CI: 1.39–2.27), progression-free survival (HR = 1.63, 95% CI: 1.34–1.93) and recurrence-free survival (HR = 1.74, 95% CI: 1.01–2.47). In addition, the level of PVT1 expression was positively related to tumor size, TNM stage, lymph node metastasis and distant metastases. Materials and Methods A systematic search was performed through the PubMed, EMBASE, Web of Science, Ovid and Cochrane library databases for eligible studies on prognostic value of PVT1 in cancers from inception up to June, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association between PVT1 expression and clinical outcomes. Conclusions PVT1 expression positively related to tumor size, TNM stages, lymph node metastasis and distant metastases, and served as a prognostic biomarker in different types of cancers.

Identification of a novel MYOC mutation in a Chinese family with primary open-angle glaucoma

PURPOSE The myocilin (MYOC) gene has been shown to be related to primary open-angle glaucoma (POAG). This study was aimed to detect the mutations in MYOC in a Chinese family with POAG. METHODS A family with four members, the parents, a son and a daughter, was enrolled in this study. All members of the family underwent the complete ophthalmologic examinations. Genomic DNA was collected from peripheral blood of all the participants. The coding sequence of MYOC was amplified by polymerase chain reaction (PCR), followed by direct DNA sequencing. RESULTS The son, who was the proband of this family, was diagnosed as early-onset POAG in both eyes. His mother was diagnosed as POAG ten years ago. A novel heterozygous missense mutation c.761C<G (p.P254R) in the MYOC gene, was identified as being co-segregated with the phenotype of this family. This mutation was detected in the two affected patients, but not present in the other normal family members or 384 normal controls. CONCLUSIONS This study provides a mutation spectrum of MYOC resulting in POAG development in a Chinese population, which may help to better understand the molecular pathogenesis and clinical diagnosis of MYOC-associated POAG.

Association of n3 and n6 polyunsaturated fatty acids in red blood cell membrane and plasma with severity of normal tension glaucoma.

AIM To determine whether red blood cell (RBC) membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) are significantly correlated with severity of normal tension glaucoma (NTG). METHODS This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean deviation (MD) score (r=0.617, P<0.001; r=0.727, P<0.001 and r=0.720, P<0.001, respectively), while the level of AA was negatively associated with the MD score (r=-0.427, P=0.001). When plasma lipids were analyzed, there was a significant positive relationship between the levels of EPA and the MD score (r=0.648, P<0.001), and the levels of AA were inversely correlated with the MD score (r=-0.638, P<0.001). CONCLUSION The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.

Association between SKIV2L polymorphism rs429608 and age-related macular degeneration: A meta-analysis

ABSTRACT Purpose: This study was conducted to comprehensively evaluate the potential association of SKIV2L polymorphism rs429608 with age-related macular degeneration (AMD) through a meta-analysis. Methods: We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for AMD genetic studies published before August 30, 2015. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for single-nucleotide polymorphisms (SNPs) using fixed-effect models or random effect models according to between-study heterogeneity. Publication bias analyses were conducted using Egger’s test. Results: A total of five studies from published articles were included, and a total number of 2789 AMD cases and 3451 healthy controls were tested in this meta-analysis. The results demonstrated that SKIV2L rs429608 is associated with AMD under allelic model (A vs. G; OR = 0.52, 95% CI 0.44–0.62, p < 0.001), heterozygous model (AG vs. GG; OR = 0.51; 95%CI, 0.38–0.68; p < 0.001; PQ = 0.48; I2 = 0) and dominant model (AA+AG vs. GG; OR = 0.49; 95%CI 0.37–0.65; p < 0.001; PQ = 0.44; I2 = 0), but not under other genetic models. Conclusions: This meta-analysis showed that SKIV2L rs429608 was statistically associated with AMD and it might exert a protective effect on AMD. Further investigations are needed to validate the association and confirm the role of SKIV2L in AMD.

Genetic variants influencing lipid levels and risk of dyslipidemia in Chinese population

Recently, several human genetic and genomewide association studies (GWAS) have discovered many genetic loci that are associated with the concentration of the blood lipids. To confirm the reported loci in Chinese population, we conducted a cross-section study to analyse the association of 25 reported SNPs, genotyped by the ABI SNaPshot method, with the blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in 1900 individuals by multivariate analysis. Logistic regression was applied to assess the association of the genetic loci with the risk of different types of dyslipidemia. Our study has convincingly identified that 12 of 25 studied SNPs were strongly associated with one or more blood lipid parameters (TC, LDL, HDL and TG). Among the 12 associated SNPs, 10 significantly influence the risk of one or more types of dyslipidemia. We firstly found four SNPs (rs12654264 in HMGCR; rs2479409 in PCSK9; rs16996148 in CILP2, PBX4; rs4420638 in APOE-C1-C4-C2) robustly and independently associate with four types of dyslipidemia (MHL, mixed hyperlipidemia; IHTC, isolated hypercholesterolemia; ILH, isolated low HDL-C; IHTG, isolated hypertriglyceridemia). Our results suggest that genetic susceptibility is different on the same candidate locus for the different populations. Meanwhile, most of the reported genetic variants strongly influence one or more plasma lipid levels and the risk of dyslipidemia in Chinese population.

Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis.

AIM To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random- effects models according to between-study heterogeneity. Publication bias analyses were conducted by Eggers test. RESULTS A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P=0.03) and in heterozygous model (CG vs GG, P=0.04), but not in other models. CONCLUSION This Meta-analysis shows that COL1A1 rs2269336 (CC vs CG+GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association.