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Yi Shi,
Bo Gong,
Lijia Chen,
Xianbo Zuo,
Xiaoqi Liu,
Pancy O S Tam,
Xiangtian Zhou,
Peiquan Zhao,
Fang Lu,
Jia Qu, [......],
Ying Lin, He Lin,
Shi Ma,
Jing Cheng,
Jiyun Yang,
Lulin Huang,
Mingzhi Zhang,
Xuejun Zhang,
Chi Pui Pang,
Zhenglin Yang
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ABSTRACT: High myopia, highly prevalent in the Chinese population, is a leading cause of visual impairment worldwide. Genetic factors play a critical role in the development of this visual disorder. Genome-wide association studies in recent years have revealed several chromosomal regions that contribute to its progression. To identify additional genetic variants for high myopia susceptibility, we used a genome-wide meta-analysis to examine the associations between the disease and 286 031 single-nucleotide polymorphisms (SNPs) in a combined cohort of 665 cases and 960 controls. The most significant SNPs (n = 61) were genotyped in a replication cohort (850 cases and 1197 controls), and 14 SNPs were further tested through genotyping in two additional validation cohorts (combined 1278 cases and 2486 controls). As a result of this analysis, four SNPs reached genome-wide significance (P < 2.0 × 10-7). The most significantly associated SNP, rs2730260 [overall P = 8.95 × 10-14; odds ratio (95% CI) =1.33 (1.23-1.44)], is located in the VIPR2 gene, which is located in the MYP4 locus. The other three SNPs (rs7839488, rs4395927 and rs4455882) in the same linkage disequilibrium block are located in the SNTB1 gene, with -P values ranging from 1.13 × 10-8 to 2.13 × 10-11. The VIPR2 and SNTB1 genes are expressed in the retina and the retinal pigment epithelium and have been previously reported to have potential functions for the pathogenesis of myopia. Our results suggest that variants of the VIPR2 and SNTB1 genes increase susceptibility to high myopia in Han Chinese.
Human Molecular Genetics 02/2013; · 7.64 Impact Factor
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Bo Gong,
Xiaoqi Liu,
Dingding Zhang,
Pu Wang,
Lulin Huang,
Ying Lin,
Fang Lu,
Shi Ma,
Jing Cheng,
Rong Chen,
Xiaobo Li, He Lin,
Guangqun Zeng,
Xiong Zhu,
Jianbin Hu,
Zhenglin Yang,
Yi Shi
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ABSTRACT: Matrix metalloproteinase 2 (MMP2) has been shown to be expressed in the human sclera, and is increased in the sclera of the eye with myopia induced by form deprivation in chicks when compared with the control eye. The purpose of this study was to examine the relationship between high myopia and MMP2 in a mainland Han Chinese population.
Four hundred unrelated patients with high myopia and 400 normal controls in a mainland Han Chinese population were studied. All the subjects were genotyped for 20 tag single nucleotide polymorphisms (SNPs) in MMP2 with the dye terminator-based SNaPshot method. The distribution of the genotypes in the cases and controls was compared with a χ(2) test. Screening for mutations in the coding regions and the adjacent intronic regions of MMP2 was performed in 200 patients with high myopia and 200 normal controls by direct sequencing.
None of the 20 tested SNPs showed significant association with high myopia in this study. Seven variations were detected upon sequencing of the coding regions and the adjacent intronic regions of MMP2 in 200 subjects with high myopia and 200 normal controls. One novel variation, c.1287G>A (p.K429K), was detected in 79 of the 200 patients with high myopia (65 heterozygous and 14 homozygous) and in 84 of the 200 controls (67 heterozygous and 17 homozygous). The c.1810G>A mutation (p. Arg500His) was detected in three of the 200 patients with high myopia but not in the controls. The five other variations, known as polymorphisms, were detected in the case and control groups.
We found no evidence that MMP2 is responsible for high myopia in these Han Chinese subjects and hence is unlikely to be important in the genetic predisposition to high myopia. Our results imply that MMP2 may not play a major role in high myopia in the Han Chinese population.
Molecular vision 01/2013; 19:121-7. · 2.20 Impact Factor
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ABSTRACT: Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient.
To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause).
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012.
We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status.
Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis.
We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60% and 100%. There was no significant difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12; 95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the pre-operative biliary drainage group (60 per 100 patients in the pre-operative biliary drainage group versus 26 per 100 patients in the direct surgery group) (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who developed serious morbidity was significantly higher in the pre-operative biliary drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not reported in any of the trials. There was no significant difference in the length of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI -1.28 to 11.02; P = 0.12) between the two groups. Trial sequential analysis showed that for mortality only a small proportion of the required information size had been obtained. There seemed to be no significant differences in the subgroup of trials assessing percutaneous compared to endoscopic drainage.
There is currently not sufficient evidence to support or refute routine pre-operative biliary drainage for patients with obstructive jaundice. Pre-operative biliary drainage may increase the rate of serious adverse events. So, the safety of routine pre-operative biliary drainage has not been established. Pre-operative biliary drainage should not be used in patients undergoing surgery for obstructive jaundice outside randomised clinical trials.
Cochrane database of systematic reviews (Online) 01/2012; 9:CD005444. · 5.72 Impact Factor
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Yi Shi,
Fang Lu,
Xin Liu,
Yao Wang,
Lulin Huang,
Xiaoqi Liu,
Wubin Long,
Bo Lv,
Kun Zhang,
Shi Ma, [......],
Bin Zhou,
Mei Hu,
Jiayun Deng,
Jianxin Zhu,
Peng Hao,
Xiao Yang,
Mingcai Zeng,
Xiaoquan Wang,
Sikui Shen,
Zhenglin Yang
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ABSTRACT: To investigate the association between variants in the HLA-DRB1 gene and Kashin-Beck disease (KBD), as well as associations of selenium and iodine deficiencies with KBD in a Tibetan population.
Fourteen single-nucleotide polymorphisms (SNPs) were genotyped around the HLA-DRB1 gene, and HLA-DRB1 allele genotyping was performed in a discovery cohort, composed of 605 patients with KBD and 393 control subjects, and/or a replication cohort, composed of 290 patients with KBD and 295 controls. Plasma concentrations of selenium and iodine were measured and compared by t-test in 299 patients with KBD and 280 controls from the same villages.
Four SNPs (rs6457617, rs6457620, rs9275295, and rs7745040) in the HLA-DRB1 gene locus were significantly associated with KBD in both the discovery cohort and replication cohort (combined cohort odds ratios [ORs] 1.307-1.402, P = 0.0039-0.0006). The protective haplotype GTCC and the risk haplotype ACGT, each generated by the 4 SNPs, showed a significant association with KBD (for GTCC, OR 0.77, P = 0.0031; for ACGT, OR 1.40, P = 0.0014). HLA-DRB1 allele genotyping revealed that the frequencies of HLA-DRB1*08 and *11 were significantly different between patients with KBD and controls (for HLA-DRB1*08, OR 0.731, P = 0.00564; for HLA-DRB1*11, OR 0.489, P = 0.000395). Moreover, plasma concentrations of selenium and iodine were significantly different between patients with KBD and controls from the same villages (P = 0.0013 and P = 1.84 × 10(-12) , respectively).
These findings, obtained in plasma samples from Tibetan patients with KBD and healthy control subjects from the same regions, confirm the role of selenium and iodine deficiencies in the development of KBD. Moreover, genetic variants in the HLA-DRB1 gene significantly increase the susceptibility to KBD in this population.
Arthritis & Rheumatism 07/2011; 63(11):3408-16. · 7.87 Impact Factor
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Yi Shi,
Jia Qu,
Dingding Zhang,
Peiquan Zhao,
Qingjiong Zhang,
Pancy Oi Sin Tam,
Liangdan Sun,
Xianbo Zuo,
Xiangtian Zhou,
Xueshan Xiao, [......],
Ying Lin,
Jiyun Yang,
Shiqiang Li,
Yunqing Ren,
Anquan Xue,
Yingchuan Fan,
Dean Li,
Chi Pui Pang,
Xuejun Zhang,
Zhenglin Yang
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ABSTRACT: High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.
The American Journal of Human Genetics 06/2011; 88(6):805-13. · 10.60 Impact Factor
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Yi Shi,
Yingrui Li,
Dingding Zhang,
Hao Zhang,
Yuanfeng Li,
Fang Lu,
Xiaoqi Liu,
Fei He,
Bo Gong,
Li Cai, [......],
Xin Jin,
Peiquan Zhao,
Yiye Chen,
Yong Zhang,
Ying Lin,
Xi Li,
Yingchuan Fan,
Huanming Yang,
Jun Wang,
Zhenglin Yang
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ABSTRACT: Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3'UTR+12 C>G, and 3'UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form.
PLoS Genetics 06/2011; 7(6):e1002084. · 8.69 Impact Factor
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ABSTRACT: In the title compound, C(12)H(12)N(2)O(4), the dihedral angle between the pyridine and enamine planes is 3.5 (3)°, while the angle between the dioxanedione (seven atoms) and enamine planes is 4.6 (3)°. The dioxane ring approximates an envelope conformation.
Acta Crystallographica Section E Structure Reports Online 01/2011; 67(Pt 2):o253. · 0.35 Impact Factor
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Dingding Zhang,
Yi Shi,
Bo Gong,
Fei He,
Fang Lu, He Lin,
Zhengzheng Wu,
Jing Cheng,
Bin Chen,
Shihuang Liao,
Shi Ma,
Jianbin Hu,
Zhenglin Yang
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ABSTRACT: Single nucleotide polymorphisms (SNPs) in the collagen type I (COL1A1) gene have been shown to be significantly associated with high myopia in a Japanese population. This present study was conducted to investigate whether COL1A1 is associated with high myopia in a Han Chinese population.
High myopia is defined by a spherical equivalent of less than or equal to -6.00 diopter sphere and an axial length longer than or equal to 26.0 mm in the affected eye. We genotyped rs2075555 and rs2269336 SNPs in COL1A1 in a Ha n Chinese group composed of 697 high myopia patients and 762 normal controls.
Neither of the two SNPs showed significant association with high myopia (p(allelic)=0.252 for rs2075555, and p(allelic)=0.699 for rs2269336).
Our study revealed that SNPs in COL1A1 are not significantly associated with high myopia in the Han Chinese population.
Molecular vision 01/2011; 17:3379-83. · 2.20 Impact Factor
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ABSTRACT: Obstruction in the biliary drainage system causes a rise in serum bilirubin levels (obstructive jaundice). Studies have shown that surgery for severe obstructive jaundice is associated with high peri-operative mortality and morbidity. Jaundice has been considered as a potential risk factor for poor outcome, and pre-operative biliary drainage has been proposed as a method of reversing the pathophysiologic disturbance seen in patients with obstructive jaundice.
To determine the benefits and harms of pre-operative biliary drainage (ie, endoscopic sphincterotomy with stent insertion or percutaneous transhepatic biliary drainage) in obstructive jaundice.
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (CHBG), the Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, the Chinese BioMedical Literature on disc (CBM disc), and the Chinese Medical Current Contents (CMCC). All databases were searched up to October 2006.
We considered for inclusion randomised clinical trials comparing biliary drainage followed by surgery and direct surgery performed for obstructive jaundice.
We collected the available data on the characteristics of the trial, methodological quality of the trials, mortality, morbidity, and hospital stay as reported in each trial. We analysed the data with both the fixed-effect and the random-effects models, using RevMan Analysis. For each outcome, we calculated the odds ratio (OR) with 95% confidence intervals (CI) based on intention-to-treat analysis.
Five trials with 320 patients (160 in each group) were included. Four trials (n = 235) compared percutaneous transhepatic biliary drainage with direct surgery, and one trial (n = 85) compared pre-operative endoscopic drainage with direct surgery. All trials were of low methodological quality. There was no significant difference in mortality (OR 1.14, 95% CI 0.60 to 2.10) between the pre-operative biliary drainage group and the direct surgery group. No significant difference was found in mortality (OR 1.16, 95% CI 0.56 to 2.41), overall morbidity (OR 1.35, 95%CI 0.48 to 3.83), and in different complications between the percutaneous transhepatic biliary drainage group and the direct surgery group. The trial comparing pre-operative endoscopic drainage and direct surgery showed no significant difference in mortality (OR 1.09, 95% CI 0.32 to 3.68), but found higher morbidity in the endoscopic drainage group. The overall hospital stay was 8 to 17 days shorter in the direct surgery group.
Our analyses neither supports nor refutes pre-operative biliary drainage for patients with obstructive jaundice needing surgery. In some specific lesion site it may cause more complications. Pre-operative biliary drainage also prolonged hospital stay and increased cost. However, the strength of evidence is low because of the poor quality of the included trials. More rigorously designed randomised clinical trials with larger sample size and advanced techniques and drugs are needed.
Cochrane database of systematic reviews (Online) 02/2008; · 5.72 Impact Factor
