血管内皮生长因子受体1基因单核苷酸多态性及吸烟与宁夏地区汉族、回族年龄相关性黄斑变性的相关性

背景 年龄相关性黄斑变性(AMD)是引起中心视力进行性退变的一类遗传病.研究证明,在不同群体中,血管内皮生长因子受体l(VEGFR1)基因多态性和AMD的发生有关联,但这些结果在不同的种族和地区却不相同. 目的 探讨VEGFR1基因单核苷酸多态性(SNPs)及吸烟与宁夏地区汉族、回族AMD的关联.方法 本研究采取病例对照关联分析的方法,收集2011年3月至2015年6月宁夏地区无亲缘关系的AMD患者432例作为AMD组,其中汉族325例,回族107例,并纳入同期中度年龄相关性白内障患者906例作为对照组,其中汉族698例,回族208例.采集所有受检者静脉血5 ml,提取全基因组DNA,筛选出VEGFR1基因上rs2281827、rs3936415、rs7337610、rs7981680、rs9554320、rs9554322、rs9582036和rs9943922共8个标签SNPs,利用MassARRAYTM飞行时间质谱系统对受检者各SNPs基因型进行分型.采用卡方检验和多因素Logistic回归分析法分析和比较汉族与回族AMD患者各位点等位基因频率及基因型频率分布情况.结果 宁夏地区汉族与回族AMD组与对照组间年龄比较差异均有统计学意义(汉族:P=0.000;回族:P=0.009);汉族AMD组与对照组间吸烟患者比例差异有统计学意义(P=0.000),吸烟是宁夏地区汉族AMD发病的风险因素[优势比(OR)=2.622,95％可信区间(CI):1.899 ～3.619].汉族和回族间AMD患者各SNPs位点等位基因频率比较差异均无统计学意义(均P＞0.05),各种族AMD组与对照组间rs7337610和rs9554322SNPs基因型分布及等位基因频率的比较差异均有统计学意义(均P=0.00),在汉族AMD组与对照组间rs9582036和rs9943922基因型分布比较差异均有统计学意义(P=0.002、0.00).回族AMD组与对照组间rs7337610、rs9554322基因型分布及等位基因频率分布差异均有统计学意义(均P=0.00),其中rs7337610的C等位基因是汉族和回族AMD发病的保护因素(OR=0.354,95％ CI:0.288 ～0.435;OR=0.446,95％CI:0.315 ～0.632),而rs9554322位点的C等位基因是汉族和回族AMD发病的危险因素(OR=1.671,95％ CI:1.234～2.262;OR=3.661,95％ C1:2.156～6.218),rs9582036位点A等位基因是汉族AMD患病的危险因素(OR=1.477,95％ CI:1.124 ～1.940). 结论 吸烟是宁夏汉族人群AMD发病的独立环境危险因素.rs9554322和rs7337610 SNPs与汉族和回族AMD发病有关联,而rs9582036及rs9943922 SNPs仅与汉族AMD发病有关联.     

LOXL1基因启动子区单核苷酸多态性与维吾尔族剥脱综合征发病的关联性研究

背景 剥脱综合征(XFS)是一种细胞外基质异常聚集的系统性疾病.研究证实,位于赖氨酰氧化酶样1(LOXL1)基因第一外显子区的单核苷酸多态性(SNPs)位点与XFS发病有一定关联,但这些研究在不同种族、国家和地区间结果并不一致.目的 探讨新疆维吾尔族人群中LOXL1基因启动子区SNPs与XFS发病的关联性.方法 采用病例对照研究设计,于2014年1-8月收集新疆地区维吾尔族无亲缘关系的152例XFS患者为XFS组,收集同期民族和性别匹配的228名眼部正常者为对照组.采集所有受检者外周血各5 ml并提取DNA,选取LOXL1基因启动子区rs12914489、rs4886467、rs4558370、rs4461027、rs4886761、rs 16958477共6个SNPs位点,利用PCR-连接酶检测反应(LDR)法对各SNPs位点进行基因分型,采用x2检验分析等位基因频率及基因型频率分布,并计算比值比(OR)值及95％可信区间(CI).结果 本研究中对照组rs12914489位点偏离Hardy-Weinberg平衡(HWE) (P=0.033),rs4886467、rs4558370、rs4461027、rs4886761、rs16958477位点均符合HWE.XFS组rs4886467等位基因G和基因型GG频率均低于对照组,差异均有统计学意义(均P=0.00),为保护因素(OR=0.54,95％CI:0.40 ～0.74,P=0.000;OR=0.51,95％ CI:0.33～0.78,P=0.001);XFS组rs4558370等位基因G和基因型GG频率均高于对照组,差异均有统计学意义(均P=0.00),二者是发病危险因素(0R=1.96,95％CI:1.23 ～3.11,P=0.004;OR=2.18,95％CI:1.31 ～3.64,P=0.002);XFS组rs4461027等位基因C和基因型CC频率均明显高于对照组,差异均有统计学意义(均P=0.00),二者是发病的危险因素(OR=2.25,95％ CI:1.67 ～3.04,P=0.000;OR=3.06,95％CI:1.89～4.96,P=0.000);XFS组rs4886761等位基因T和基因型TT频率均高于对照组,差异均有统计学意义(均P=0.00),二者是发病危险因素(OR=2.44,95％ CI:1.79～3.33,P=0.000;OR=3.02,95％CI:1.63～5.60,P=0.000);XFS组rs16958477位点等位基因C和基因型CC频率均高于XFS组,差异均有统计学意义(均P=0.00),二者是发病的危险因素(OR=2.00,95％CI:1.47 ～2.71,P=0.000;OR=2.37,95％CI:1.31～4.27,P=0.004).结论 新疆维吾尔族人群LOXL1基因启动子区的SNPs与新疆维吾尔族XFS发生存在关联,其中rs4886467位点是发病的保护因素,rs4558370、rs4461027、rs4886761和rs16958477位点是XFS发生的危险因素.     

超氧化物歧化酶与年龄相关性白内障关系的研究

目的 探讨超氧化物歧化酶(superoxide dismutase,SOD)基因多态性与年龄相关性白内障发生的关系.方法 年龄相关性白内障病例415例为白内障组,其中121例为皮质性白内障,109例为核性白内障,59例为后囊下白内障,126例为混合性白内障.年龄、性别匹配的386例健康者作为对照组.以聚合酶链反应-限制性片段长度多态性的方法检测SOD1-251 A/G基因多态分型,以x2检验比较SOD1多态基因型在白内障组与对照组之间分布的差异.结果 白内障组SOD1-251 G/G基因型频率明显高于对照组(P=0.012,OR=1.642,95％ CI为1.129～ 2.389),可能是白内障发展的危险因素;SOD1-251 A/A基因型明显低于对照组(P=0.001,OR=0.613,95％ CI为0.461 ～0.817),可能是对照组的一个保护因素;两组中SOD1-251A/A中的G型等位基因频率差异有统计学意义(P =0.001,OR=1.479,95％ CI为1.208～1.810).相对于对照组,皮质性和混合性白内障病例中SOD1-251 G/G基因型频率(分别为P=0.031,OR=1.805,95％ CI为1.076 ～3.026;P =0.002,OR=2.229,95％ CI 为1.364～3.645)和A/A基因型频率(分别为P=0.026,OR=0.608,95％ CI为0.396～0.933;P =0.001,OR =0.474,95％ CI为0.305～0.734)存在显著不同.结论 SOD1-251 G/G基因型可能是导致白内障的一个危险因素.     

MCP-1基因-2518A/G多态性与葡萄膜炎易感性的Meta分析

背景 近年来研究表明,单核细胞趋化蛋白1(MCP-1)基因多态性与葡萄膜炎易感性密切相关,然而目前国内外关于MCP-1基因-2518A/G多态性与葡萄膜炎发病风险的相关性尚未有一致结论.目的 系统评价MCP-1基因-2518 A/G多态性与葡萄膜炎易感性的关系.方法 按照检索策略,计算机检索PubMed、Embase、Web of Science、中国知网(CNKI)、维普网(VIP)、万方数据及中国生物医学文献数据库(CBD),检索时限为建库起至2014年3月,收集关于MCP-1基因-2518A/G多态性与葡萄膜炎发病风险的相关文献,按照纳入及排除标准筛选文献、提取数据资料,并对纳入研究的文献进行质量评价.采用RevMan 5.2及Stata12.0软件进行Meta分析,计算合并效应量优势比(OR)值及其95％可信区间(CI),并进行发表偏倚及敏感性分析.结果 共纳入8篇研究文献,累积病例1 197例,对照1 570例.MCP-1基因-2518A/G G和A、GG和AA及GG和AG+AA基因型与总体葡萄膜炎发病风险均无明显相关性(均P＞0.05),GG+AG和AA基因型与总体葡萄膜炎发病风险具有显著相关性(P=0.01,OR=1.25,95％C1:1.06～1.48),而敏感性分析结果显示二者无明显相关性(P=0.19,OR=1.16,95％ CI:0.93～1.45).按葡萄膜炎类型进行亚组分析结果显示,携带等位基因G、GG基因型的个体罹患前葡萄膜炎的风险明显增高(G和A:P=0.01,OR=1.49,95％CI:1.16 ～1.90;GG和AA:P=0.01,OR=2.09,95％CI:1.21～3.61;GG+AG和AA:P=0.01,OR=1.58,95％ CI:1.12～2.23;GG和AG+AA:P=0.01,OR=1.78,95％CI:1.12 ～2.83),且GG+AG和AA基因型个体罹患白塞病的风险也明显增高(P=0.04,OR=1.35,95％CI:1.01～1.79),而与其他类型葡萄膜炎发病风险无明显相关(P＞0.05).按种族进行亚组分析结果显示,在黄种人群中,携带等位基因G、GG基因型的个体罹患葡萄膜炎的风险明显增高(G和A:P=0.04,OR=1.15,95％CI:1.01～1.32;GG和AA:P=0.04,OR=1.32,95％ CI:1.02 ～1.71;GG+AG和AA:P=0.01,OR=1.36,95％CI:1.09～1.70),而在白种人群中等位基因G、GG基因型与葡萄膜炎均无明显相关(均P＞0.05).结论 MCP-1基因-2518A/G多态性与白塞病、前葡萄膜炎及黄种人群葡萄膜炎易感性有关,GG基因型及等位基因G可能是白塞病、前葡萄膜炎及黄种人群葡萄膜炎易感的危险因素.     

候选基因多态性与糖尿病视网膜病变相关性的Meta分析

目的 候选基因多态性位点与2型糖尿病患者（type 2 diabetes mellitus，T2DM）的糖尿病视网膜病变（diabetes retinopathy，DR）相关性的Meta分析。设计 Meta分析。研究对象  T2DM的DR候选基因多态性的英文或中文文献。方法 在Pubmed（National Center for Biotechnology Information）、ISI（Web of Kowledge）、Embase和中国知网（China National Knowledge Internet，CNKI）4个数据库中，系统性检索、收集2019年1月1日以前以中文和英文发表的关于色素上皮源性因子（pigment epithelium derived factor，PEDF）、肿瘤坏死因子（tumor necrosis factor-α，TNF-α）和对氧磷酶-1（paraoxonase 1，PON1）三个基因的多态性位点与DR相关性的文献。采用Stata 12.0软件计算合并优势比（pooled odds ratio，pooled OR），分析组间异质性（Pheterogeneity）和发表偏倚（publication bias）。主要指标 OR值、组间异质性，发表偏倚。结果 共13篇研究纳入本Meta分析，包括2729例DR和3420例糖尿病对照。PEDF基因的 rs12948385位点（显性模型：OR=1.371，95%CI：1.072~1.755，P=0.012；等位基因模型：OR=1.266，95%CI：1.028~1.560，P=0.027）和PON1基因的L55M位点（隐性模型：OR=2.998，95%CI：1.282~7.010，P=0.011）与DR相关；TNF-α基因的rs1800629位点与PDR相关（等位基因模型：OR=1.291，95%CI：1.019~1.636，P=0.034）。结论  PEDF基因的 rs12948385位点、PON1基因的L55M位点可能与DR相关；TNF-α基因的rs1800629位点可能与PDR相关。     

CYP1A1 T6235C基因多态性与头颈恶性肿瘤易感性的Meta分析

目的 探讨Ⅰ相代谢酶细胞色素P450 1A1(CYP1A1) T6235C基因多态性与头颈恶性肿瘤易感性的关系.方法 检索PubMed、EMBASE、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)已发表的关于CYP1A1 T6235C基因多态性与头颈恶性肿瘤易感性的相关研究,筛选出符合条件的文献,应用Meta分析软件对各项研究进行异质性检验,计算合并OR值及其95％可信区间(CI),并行敏感度分析和发表偏倚的评估.结果 共16篇文献纳入本研究(病例组数2 754例;对照组数2 807例).Meta分析结果显示:CYP1A1 T6235C基因多态性与头颈恶性肿瘤有明显易感性(CC versus TT:OR =3.216,95％ CI 2.388～4.331;CC versus CT/TT:OR=2.496,95％ CI1.994～3.124;CC versus CT:OR=1.993,95％ CI 1.476 ～2.692; CC/CTversus TT:OR=1.573,95％ CI1.230～2.013).根据种族进行分层分析发现亚洲人群有明显易感性.结论 CYP1A1 T6235C基因多态性与头颈恶性肿瘤易感性间存在明显易感性.     

补体因子H基因单核苷酸多态性与渗出型老年性黄斑变性易感性的相关性研究

目的 探讨渗出型老年性黄斑变性(AMD)易感性与补体因子H(CFH)基因单核苷酸(SNP)多态性的相关性。方法 病例对照研究。136例渗出型AMD患者（AMD组）和年龄、性别与之匹配的140名正常健康者（对照组）纳入研究。取得所有受检者的知情同意后,抽取晨起空腹肘静脉血4 ml,提取基因组DNA。采用多聚酶链反应和特异性限制内切酶消化法检测CFH Y402H(rs1061170)、CFH-257C＞T(rs3753394)及CFH IVS15(rs1329428)的基因型和等位基因。采用SHEsis软件构建单倍型,对比分析两组CFH基因SNP不同单倍型的频率。分析CFH基因SNP不同等位基因、基因型和单倍型与渗出型AMD的相关性。结果 CFH Y402H(rs1061170)存在TT、TC、CC 3种基因型,等位基因位于位点T、C;CFH-257C＞T(rs3753394)存在CC、CT、TT 3种基因型,等位基因位于位点C、T;CFH IVS15(rs1329428)存在AA、AG、GG 3种基因型,等位基因位于位点A、G。AMD组、对照组CFH基因型和等位基因频率比较,差异均有统计学意义(P＜0.05)。CFH Y402H (rs1061170)的杂合子基因型TC、CFH-257C＞T(rs3753394)的纯合子基因型TT及CFH IVS15(rs1329428)的纯合子基因型GG均与渗出型AMD有相关性(OR=4.11,2.55,3.11;P＜0.05);等位基因T、C、G为风险等位基因(OR=3.14,1.72,1.79;P＜0.05)。AMD组和对照组单倍型TCG、CTG及CTA频率间差异有统计学意义(X2=10.53,6.60,32.82;P＜0.05);其余单倍型频率间差异无统计学意义(P＞0.05)。结论 CFH基因SNP多态性与渗出型AMD易感性有关。     

早产儿视网膜病变易感性与血管内皮生长因子-A+405和-A936基因多态性的相关性

目的 探讨早产儿视网膜病变(ROP)易感性与血管内皮生长因子(VEGF)-A+ 405和VEGF-A936基因多态性的相关性。方法 99例ROP患儿（ROP组）和80例非ROP早产儿（对照组）纳入本研究。两组受检者的出生年龄、出生体重及给氧时间之间差异均无统计学意义(P＞0.05)。取得所有受检者监护人的知情同意后,抽取外周静脉血2 ml。采用焦磷酸测序法检测VEGF-A+ 405和VEGF-A936基因多态性表型、等位基因和基因频率。分析ROP与VEGF-A+ 405和VEGF-A936基因多态性的相关性。结果 VEGF-A+ 405存在CC、GG、CG 3种基因型,VEGF-A936存在CC、CT 2种基因型。ROP组VEGF-A+405位点C、G等位基因分别为92、106,基因频率分别为46.5％,53.5％;对照组VEGF-A+405位点C、G等位基因分别为90、70,基因频率分别为56.2％,43.8％;两组比较,差异无统计学意义(X2=3.396,P=0.066)。相关性分析发现,VEGF-A+ 405基因多态性与ROP发生无相关性(OR=0.675,OR95％ CI=0.444,1.026)。ROP组VEGF-A936位点T、C等位基因分别为32、166,基因频率分别为16.2％,83.8％;对照组VEGF-A936位点T、C等位基因分别为16、144,基因频率分别为1o.o％,90.0％;两组比较,差异无统计学意义(X2 =2.894,P=0.089)。相关性分析发现,VEGF-A936基因多态性与ROP发生无相关性(OR=0.768,OR95％ CI=0.711,0.829)。结论 VEGF-A+ 405和VEGF-A936基因多态性与ROP易感性无关。     

血管内皮生长因子基因多态性与渗出型老年性黄斑变性的相关性研究

老年性黄斑变性(AMD)是导致50岁以上老年人群中不可逆盲的最常见原因[1]。渗出型AMD的发病机制研究表明,多种血管因子特别是血管内皮生长因子( VEGF)参与新生血管的形成。目前通过抑制VEGF活性能够使约40％渗出型AMD患眼的视力得到有效改善[2]。有研究报道,AMD患者具有VEGF基因多态性,位于基因3＇端非编码区的+936C/T(rs3025039),与台湾AMD患者的患病风险相关[3]。但目前对于VEGF基因变量与渗出型AMD的患病风险的相关性尚存在争议。我们对VEGF基因多态性与居住在中国大陆的渗出型AMD的疾病易感性的相关性进行研究：选择4个能够影响VEGF转录表达的单核苷酸多态性(SNP)[35],rs833061,rs2010963,rs1413711和rs3025039,并通过用以覆盖VEGF基因的所有常见变量的标签SNP(tSNP)技术以期寻找与渗出型AMD疾病易感性相关的新的VEGF基因变量。     

新疆维吾尔族剥脱综合征患者LOXL1基因编码区位点多态性研究

目的 研究新疆维吾尔族人群中剥脱综合征(exfoliation syndrome,XFS)患者类赖氨酰氧化酶l(lysyl oxidase-like 1,LOXL1)基因编码区位点的多态性.方法 选取152例维吾尔族XFS患者作为病例组和228名维吾尔族健康者作为对照组,抽取患者和健康对照组外周血2 mL,用imLDRTM多重SNP分型试剂盒对380个样本进行3个SNPs位点分型,对比分析病例组和对照组每个SNP位点的等位基因、基因型和单倍体多态性的差异.结果 病例组的rs1048661:等位基因G与基因型GG频率高于对照组,差异有统计学意义,为发病的危险因素[0R(95％ CI):2.24(1.56 ～3.23)],0R(95％ CI):2.51(1.63 ～3.89)];病例组的rs3825942:等位基因G与基因型GG频率高于对照组,差异有统计学意义,为发病的危险因素[OR(95％CI):4.60(2.56 ～8.28),0R(95％ CI):6.17(3.22～ 11.84)].病例组的rs2165241:等位基因T与基因型TT的频率高于对照组,差异有统计学意义,为发病的危险因素[OR(95％CI):2.18(1.61 ～2.94),OR(95％ CI):2.77(1.62 ～4.74)].3个位点组成的单倍型G-G-T与疾病的发生密切相关[OR(95％ CI):2.20(1.63～2.96),P＜0.05].结论 LOXL1基因编码区的rs1048661、rs3825942、rs2165241位点与维吾尔族人群中XFS的发病密切相关.     

Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

AIM: To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS: A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.     

Association between complement factor I gene polymorphisms and the risk of age-related macular degeneration: a Meta-analysis of literature

AIM: To systematically review the association between complement factors I (CFI) polymorphisms and age-related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD. METHODS: Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger’s test, Begg’s rank correlation methods were used to evaluate for publication bias. RESULTS: Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T>C and 3 articles focus on rs2285714C>T). For rs10033900T>C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%CI: 0.72-0.99, P=0.04; TC versus TT models OR=0.89, 95%CI: 0.88-0.99, P=0.04; CC versus TT models, OR=0.76, 95%CI: 0.60-0.98, P=0.03; TC+CC versus TT models, OR=0.81, 95%CI:0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C>T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and TC+CC (OR=1.34, 95%CI: 1.09-1.63, P=0.004; OR=1.50, 95%CI: 1.25-1.80, P<0.0001). CONCLUSION: This Meta-analysis suggests that CFI rs10033900T>C and rs2285714C>T polymorphisms may contribute to AMD.     

Complement factor B polymorphism (rs641153) and susceptibility to age-related macular degeneration:evidence from published studies

AIM:To determine whether single nucleotide polymorphism (SNP) rs641153 is associated with the risk of age-related macular degeneration (AMD), we performed a systematic meta-analysis of 15 eligible studies. SNP in the complement factor B (CFB) gene is considered to have significant association with AMD susceptibility, but there is great discrepancy in these results.METHODS: The eligible studies were identified by searching the databases of PubMed, EMBASE, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. All data were analyzed using Stata software.RESULTS:The association between rs641153 and AMD risk was statistically significant under the homozygous model (AA vs GG:OR=0.26, 95%CI=0.15-0.45, Ph=0.973, I²=0.0%, fixed effects), dominant model (AA+GA vs GG:OR=0.49, 95%CI=0.40-0.59, Ph=0.004, I²=56.4%, random effects) and recessive model (AA vs GA+GG:OR=0.30, 95%CI=0.17-0.51, Ph=0.983, I²=0.0%, fixed effects). The same results were also observed in the stratified analyses by ethnicity, source of control and sample size.CONCLUSION:Our meta-analysis suggests that rs641153 in the CFB gene may play a protective role in AMD susceptibility, the late AMD in particular, both in Caucasians and in Asians.     

Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

AIM:To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).METHODS:Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored.RESULTS:Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05). A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR) in Asians only in dominant model (GG+AG vs AA) with pooled OR of 0.729 (95%CI:0.564-0.942, P=0.016, Pheterogeneity=0.143), however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI:0.898-1.545, P=0.236, Pheterogeneity=0.248) or allelic model (G vs A; OR=0.769, 95% CI:0.576-1.026, P=0.074, Pheterogeneity=0.094). No publication bias was found by Funnel plot, Begg's and Egger's test.CONCLUSION:This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.     

Association of COL1A1 polymorphism with high myopia: a Meta-analysis

AIM: To investigate the association between collagen type I alpha 1 (COL1A1) gene and high myopia. METHODS: In this Meta-analysis, we examined 5 published case-control studies that involved 1942 high myopia cases and 2929 healthy controls to assess the association between the COL1A1 rs2075555 polymorphism and high myopia risk. We calculated the pooled odds ratios (ORs) of COL1A1 rs2075555 polymorphism in high myopia cases vs healthy controls to evaluate the strength of the association. RESULTS: Overall, there was no significant difference both in the genotype and allele distributions of COL1A1 rs2075555 polymorphism between high myopia cases and healthy controls: CC vs AA OR=1.10, 95% confidence interval (CI)=0.76-1.58; AC vs AA OR=0.98, 95%CI 0.80-1.20; CC/AC vs AA/OR=1.01, 95%CI 0.84-1.22; CC vs AC/AA OR=1.06, 95%CI=0.93-1.20; C vs A OR=1.06, 95%CI 0.91-1.23). In addition, in the stratified analyses by ethnicity, no significant associations were found in any genetic model both in European and Asia cohorts. CONCLUSION: Our results indicate that the COL1A1 rs2075555 polymorphism may not affect susceptibility to high myopia.     

Complement factor B polymorphism (rs641153) and susceptibility to age-related macular degeneration:evidence from published studies

AIM

To determine whether single nucleotide polymorphism (SNP) rs641153 is associated with the risk of age-related macular degeneration (AMD), we performed a systematic meta-analysis of 15 eligible studies. SNP in the complement factor B (CFB) gene is considered to have significant association with AMD susceptibility, but there is great discrepancy in these results.

METHODS

The eligible studies were identified by searching the databases of PubMed, EMBASE, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. All data were analyzed using Stata software.

RESULTS

The association between rs641153 and AMD risk was statistically significant under the homozygous model (AA vs GG:OR=0.26, 95%CI=0.15-0.45, P_h=0.973, I²=0.0%, fixed effects), dominant model (AA+GA vs GG:OR=0.49, 95%CI=0.40-0.59, P_h=0.004, I²=56.4%, random effects) and recessive model (AA vs GA+GG:OR=0.30, 95%CI=0.17-0.51, P_h=0.983, I²=0.0%, fixed effects). The same results were also observed in the stratified analyses by ethnicity, source of control and sample size.

CONCLUSION

Our meta-analysis suggests that rs641153 in the CFB gene may play a protective role in AMD susceptibility, the late AMD in particular, both in Caucasians and in Asians.     

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

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; P_Q = 0.48; I² = 0) and dominant model (AA+AG vs. GG; OR = 0.49; 95%CI 0.37–0.65; p < 0.001; P_Q = 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.     

Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration

Background: To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD).

Methods: A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case–control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software.

Results: The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10^?4; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11–41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71–0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed.

Conclusions: The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.     

Risk factors for Age-related Macular Degeneration in a Greek population: The Thessaloniki Eye Study

Purpose: To assess the association of potential risk factors with early and late age-related macular degeneration (AMD) in the Thessaloniki Eye Study (TES) population

Design: Population-based, cross-sectional study of subjects over age of 60 living in Thessaloniki, Greece

Methods: Subjects without any AMD features and subjects with early and late AMD (neovascular AMD or geographic atrophy) were identified in the TES cohort using standardized procedures and masked grading of stereo color fundus photos. Demographic, lifestyle, systemic and other ophthalmic covariates were also collected during a detailed examination process. Their association with AMD was investigated using univariate and multivariate adjusted logistic regression models.

Results: Among the 2108 participants with gradable photos, the grading process identified 1204 subjects with no AMD, 848 subjects with early AMD, and 56 subjects with late AMD (24 with geographic atrophy and 32 with neovascular AMD). In multivariate analysis, compared to no AMD, late AMD was positively associated with older age (OR:1.16; 95%CI:1.10–1.22 per year of age), current smoking (smoking vs. never smoking, OR:2.34; 95%CI:1.12–4.90), prior cataract surgery (cataract surgery vs. no cataract surgery OR:2.06; 95%CI:0.96–4.40), marital status (divorced/separated vs. married, OR:3.10; 95%CI:1.08–8.93) and with 60% lower odds when sleeping in the afternoon (yes vs. no, OR:0.40; 95%CI:0.22–0.72). Early AMD was positively associated with older age (OR: 1.03; 95%CI:1.01–1.05 per year of age) and negatively with higher pulse pressure (OR:0.99; 95%CI:0.98–0.99 per mmHg).

Conclusions: In TES, apart for well-known risk factors for AMD like age, smoking, and cataract surgery, two novel behavioral risk factors for prevalent late AMD were suggested. Sleeping in the afternoon was associated with 60% decreased odds for late AMD and 67% decreased odds for neovascular AMD. Being divorced/separated compared to married was associated with 3-fold higher odds for late AMD. Large longitudinal population-based studies will be necessary to further establish the potential late AMD risk effects of these two novel factors, to demonstrate potential implications of underlying pathogenetic mechanisms, and to explore preventive measures and therapeutic targets.     

Matrix metalloproteinase-1 rs1799750 polymorphism and glaucoma: A meta-analysis

Purpose: Several studies indicated that -1607 1G/2G (rs1799750) polymorphism in matrix metalloproteinase-1 (MMP-1) promoter was correlated with glaucoma susceptibility, but the results remain controversial. We performed a meta-analysis to assess whether rs1799750 confers glaucoma risk.

Methods: Eligible studies were retrieved by systematically searching Pubmed, Embase, Web of Science, and Chinese Biomedical database. The degree of correlation was expressed as odds ratios (ORs) and 95% confidence interval (CI). The measurements were pooled by fixed effect model or random effect model.

Results: This meta-analysis included five case-control studies involving 1261 patients with glaucoma and 1089 controls. The pooled results showed a significant association between rs1799750 and glaucoma under the homozygote (OR = 1.71, 95% CI 1.12–2.62, p = 0.014), recessive (OR = 1.64, 95% CI 1.20–2.25, p = 0.002), and allelic (OR = 1.35, 95% CI 1.05–1.72, p = 0.017) models. Subgroup analyses showed that the rs1799750 was significantly associated with primary angle closure glaucoma under homozygote (OR = 2.23, 95% CI 1.03–4.83, p = 0.043) and allelic (OR = 1.61, 95% CI 1.07–2.42, P = 0.021) models, while it was significantly associated with primary open angle glaucoma (OR = 1.64, 95% CI 1.05–2.56, p = 0.030) and exfoliation glaucoma (OR = 1.42, 95% CI 1.02–1.97, p = 0.036) under recessive models. No evidence of publication bias was detected.

Conclusions: Meta-analysis of existing data showed that rs1799750 may affect individual susceptibility to glaucoma. Nevertheless, more studies with large sample size and various ethnicities are warranted in light of the limited studies.