乙二醛酶Ⅰ基因多态性与动脉粥样硬化性脑梗死的关系

Relationship between glyoxalase Ⅰ gene polymorphisms and atherosclerotic cerebral infarction

目的 探讨乙二醛酶Ⅰ（glyoxalase Ⅰ,GLO1）基因多态性和动脉粥样硬化性脑梗死（ACI）易患性的关系.方法 采用SNaPshot技术对300例ACI患者（病例组）和300名健康体检者（对照组）的GLO1基因多态性位点rs1 130534和rs1049346进行基因型检测,采用荧光定量PCR方法分别检测50例病例和50名对照的GLO1基因mRNA相对表达水平.结果 病例组rs1049346位点CC、CT和TT基因型频率分别是9.3％、42.7％和48.0％,对照组分别是14.0％、47.7％和38.3％;病例组rs1049346位点C和T等位基因频率分别是30.7％和69.3％,对照组分别是37.8％和62.2％;两组基因型和等位基因频率分布比较,差异均有统计学意义（基因型：x2=6.877,P=0.032;等位基因：x2=6.842,P=0.009）.病例组rs1130534位点AA、AT和TT基因型频率分别是52.0％、42.0％和6.0％,对照组分别是60.0％、33.7％和6.3％;病例组rs1130534位点A和T等位基因频率分别是73.0％和27.0％,对照组分别是76.8％和23.2％;两组rs1130534位点的基因型和等位基因频率分布比较,差异均无统计学意义（P＞0.05）.病例组的A-T和T-T单倍体型（rs1130534-rs1049346）频率均明显高于对照组,差异有统计学意义（分别为42.3％、39.0％,x2=4.733,P=0.030;分别为27.0％、23.2％,x2=5.699,P=0.017）.病例组GLO1基因mRNA相对表达量低于对照组（Mann-Whitney U=911.5,P=0.020）.结论 GLO1基因rs1049346位点单核苷酸多态性与ACI易患性相关.

Objective To investigate the association of glyoxalase Ⅰ （GLO1） gene polymorphisms with susceptibility to atherosclerotic cerebral infarction （ACI）.Methods Single nucleotide polymorphisms （SNPs） rs1130534 and rs1049346 in the GLO1 gene were genotyped in 300 ACI patients and 300 healthy controls using the SNaPshot technique.Additionally,quantitative real-time PCR was employed to determine the GLO1 expression levels in 50 ACI patients and 50 healthy controls,respectively.Results In terms of the rs1049346 polymorphism,the respective frequencies of CC,CT and TT genotypes were 9.3％,42.7％ and 48.0％ in the ACI patients,and 14.0％,47.7％ and 38.3％ in the control group.The respective frequencies of C and T alleles were 30.7％ and 69.3％ in the ACI patients,and 37.8％ and 62.2％ in the control group.There were statistically significant differences in the genotype and allele frequencies of rs1049346 between the ACI patients and controls （genotype：x2 =6.877,P =0.032;allele：x2 =6.842,P=0.009）.For rs1130534,the respective frequencies of AA,AT and TT genotypes were 52.0％,42.0％ and 6.0％ in the ACI patients,and 60.0％,33.7％ and 6.3％ in the control group.The respective frequencies of A and T alleles were 73.0％ and 27.0％ in the ACI patients,and 76.8％ and 23.2％ in the control group.However,no statistically significant differences were found in the distribution of genotypes or alleles of the rs1130534 SNP between the ACI patients and controls （all P ＞ 0.05）.The results of haplotype analysis revealed that the frequencies of the A-T and T-T （rs1130534-rs1049346） haplotypes in the ACI patients were all significantly higher compared to the controls （42.3％ vs 39.0％,x2 =4.733,P =0.030;27.0％ vs 23.2％,x2 =5.699,P =0.017）.Additionally,the GLO1 expression levels in the ACI patients were significantly lower than that in the healthy controls （Mann-Whitney U =911.5,P =0.020）.Conclusion The results indicate that the rs1049346 polymorphism of GLO1 gene is associated with the susceptibility to ACI.