目的采用Meta分析法综合评价对氧磷脂酶1 192Gln/Arg(PON1 Q192R)基因多态性与2型糖尿病并发冠心病的相关性。方法截至2017年3月,在Pubmed、Embase、Web of Science、中国知网、万方等数据库可检索到的已发表论文,由两位评价者根据纳入...目的采用Meta分析法综合评价对氧磷脂酶1 192Gln/Arg(PON1 Q192R)基因多态性与2型糖尿病并发冠心病的相关性。方法截至2017年3月,在Pubmed、Embase、Web of Science、中国知网、万方等数据库可检索到的已发表论文,由两位评价者根据纳入排除标准独立筛选和评价文献质量。采用Rev Man5.3和Stata12.0软件进行Meta分析,计算合并比值比(odds ratio,OR)及其95%可信区间(confidence intervals,CI),并进行敏感度分析和发表偏倚评估。结果 9个病例-对照研究纳入本研究,包括1353例病例组(2型糖尿病并发冠心病组)和1360例对照组(单纯2型糖尿病组)。Meta分析结果显示,与单纯糖尿病组比较,5种基因模型均提示PON1Gln/Arg基因多态性和2型糖尿病并发冠心病显著相关[等位基因模型:R vs Q,OR=1.50,95%CI(1.23~1.83);纯合子基因模型:RR vs QQ,OR=2.28,95%CI(1.52~3.42);杂合子基因模型:QR vs QQ,OR=1.42,95%CI(1.18~1.71);显性基因模型:RR+RQ vs QQ,OR=1.59,95%CI(1.33~1.89);隐性基因模型:RR vs RQ+QQ,OR=1.74,95%CI(1.24~2.45)]。人口学的亚组分析提示,对氧磷脂酶1 192Gln/Arg基因多态性与2型糖尿病并发冠心病的相关性在亚洲和高加索人群中比较,差异无统计学意义。敏感度结果显示,合并的结果是稳定可靠的,漏斗图检测未发现发表偏倚。结论 PON1 192Gln/Arg基因多态性与2型糖尿病并发冠心病风险呈显著相关性,携带R等位基因的2型糖尿病人群相对于携带Q等位基因者,可能更易并发冠心病。展开更多
Background and Purpose -The paraoxonases are involved in protecting low-density lipoprotein (LDL) from lipid oxidation. Paraoxonase 1 (PON1) was implicated in susceptibility to coronary artery disease and stroke in pr...Background and Purpose -The paraoxonases are involved in protecting low-density lipoprotein (LDL) from lipid oxidation. Paraoxonase 1 (PON1) was implicated in susceptibility to coronary artery disease and stroke in previous studies. We evaluated, in a comprehensive way, all 3 paraoxonase genes for association with stroke observed in the Cholesterol and Recurrent Events (CARE) trial. Methods - Over 2500 subjects enrolled in the CARE trial were genotyped for 14 single nucleotide polymorphisms, including 7 newly identified in this study, in the 3 paraox onase genes. Results -A glutamine (Gln)/arginine (Arg) polymorphism at amino ac id residue 192 in PON1 was significantly associated with stroke (P=0.003 in mult ivariate analysis, including age, sex, LDL, hypertension, diabetes, smoking, and pravastatin treatment as covariates). The odds ratios were 2.28 (95%CI, 1.38 t o 3.79) for Gln/Arg heterozygotes and 2.47 (95%CI, 1.18 to 5.19) for Arg/Arg ho mozygotes compared with Gln/Gln homozygotes. These results are consistent with 2 of 3 other published studies. In combined analysis of all 4 studies, the associ ation between Gln192Arg SNP and stroke was highly significant (χ28df=45.58, P < 0.000001). Sequence analysis of the PONl gene from seventy stroke cases reveale d a novel nonsense mutation at codon 32 in one stroke case, which was not detect ed in over 2500 unaffected individuals. Polymorphisms in the PON2 and PON3 genes were not associated with stroke. Conclusions -These results suggest that Gln19 2Arg genotype is an important risk factor for stroke.展开更多
文摘目的采用Meta分析法综合评价对氧磷脂酶1 192Gln/Arg(PON1 Q192R)基因多态性与2型糖尿病并发冠心病的相关性。方法截至2017年3月,在Pubmed、Embase、Web of Science、中国知网、万方等数据库可检索到的已发表论文,由两位评价者根据纳入排除标准独立筛选和评价文献质量。采用Rev Man5.3和Stata12.0软件进行Meta分析,计算合并比值比(odds ratio,OR)及其95%可信区间(confidence intervals,CI),并进行敏感度分析和发表偏倚评估。结果 9个病例-对照研究纳入本研究,包括1353例病例组(2型糖尿病并发冠心病组)和1360例对照组(单纯2型糖尿病组)。Meta分析结果显示,与单纯糖尿病组比较,5种基因模型均提示PON1Gln/Arg基因多态性和2型糖尿病并发冠心病显著相关[等位基因模型:R vs Q,OR=1.50,95%CI(1.23~1.83);纯合子基因模型:RR vs QQ,OR=2.28,95%CI(1.52~3.42);杂合子基因模型:QR vs QQ,OR=1.42,95%CI(1.18~1.71);显性基因模型:RR+RQ vs QQ,OR=1.59,95%CI(1.33~1.89);隐性基因模型:RR vs RQ+QQ,OR=1.74,95%CI(1.24~2.45)]。人口学的亚组分析提示,对氧磷脂酶1 192Gln/Arg基因多态性与2型糖尿病并发冠心病的相关性在亚洲和高加索人群中比较,差异无统计学意义。敏感度结果显示,合并的结果是稳定可靠的,漏斗图检测未发现发表偏倚。结论 PON1 192Gln/Arg基因多态性与2型糖尿病并发冠心病风险呈显著相关性,携带R等位基因的2型糖尿病人群相对于携带Q等位基因者,可能更易并发冠心病。
文摘Background and Purpose -The paraoxonases are involved in protecting low-density lipoprotein (LDL) from lipid oxidation. Paraoxonase 1 (PON1) was implicated in susceptibility to coronary artery disease and stroke in previous studies. We evaluated, in a comprehensive way, all 3 paraoxonase genes for association with stroke observed in the Cholesterol and Recurrent Events (CARE) trial. Methods - Over 2500 subjects enrolled in the CARE trial were genotyped for 14 single nucleotide polymorphisms, including 7 newly identified in this study, in the 3 paraox onase genes. Results -A glutamine (Gln)/arginine (Arg) polymorphism at amino ac id residue 192 in PON1 was significantly associated with stroke (P=0.003 in mult ivariate analysis, including age, sex, LDL, hypertension, diabetes, smoking, and pravastatin treatment as covariates). The odds ratios were 2.28 (95%CI, 1.38 t o 3.79) for Gln/Arg heterozygotes and 2.47 (95%CI, 1.18 to 5.19) for Arg/Arg ho mozygotes compared with Gln/Gln homozygotes. These results are consistent with 2 of 3 other published studies. In combined analysis of all 4 studies, the associ ation between Gln192Arg SNP and stroke was highly significant (χ28df=45.58, P < 0.000001). Sequence analysis of the PONl gene from seventy stroke cases reveale d a novel nonsense mutation at codon 32 in one stroke case, which was not detect ed in over 2500 unaffected individuals. Polymorphisms in the PON2 and PON3 genes were not associated with stroke. Conclusions -These results suggest that Gln19 2Arg genotype is an important risk factor for stroke.
