上海市438例体检者同型半胱氨酸水平与代谢关键酶基因多态性的关联分析

Correlation of homocysteine levels with gene polymorphisms of metabolic enzyme in 438 adults taking physical examination in Shanghai,China

目的研究上海市438例体检者的同型半胱氨酸(Hcy)水平与代谢相关酶基因多态性的关联。方法酶循环法检测上海市仁爱医院438例健康体检者的血浆总Hcy(tHcy)、电化学发光法检测叶酸,连接酶检测反应(LDR)进行基因分型。比较不同基因型的Hcy水平,并分析代谢相关酶的基因多态性与tHcy水平的关联。结果高同型半胱氨酸血症(HHcy)检出率为28.54%(125/438)。MTHFR C677T不同基因型的tHcy水平间差异有统计学意义(P<0.001)。MTHFR A1298C杂合型CA降低HHcy的患病风险[OR=0.49,95%CI:(0.26,0.92),P=0.027]。MTHFR C677T杂合型CT和突变纯合型TT均增加HHcy的患病风险[OR=2.15,95%CI:(1.06,4.36),P=0.035;OR=7.58,95%CI:(3.15,18.22),P<0.001]。MTR G905A、MTRR A66G、MTRR Ac.56+781C、MTR A2756G、CBSC551G并未发现与HHcy的患病风险有关联。结论 MTHFRC677T杂合型CT和突变纯合型TT是HHcy患病的风险基因型;MTHFR A1298C杂合型CA可能有助于降低HHcy风险。

Objective To investigate the correlation of homocysteine （Hcy） level with gene polymorphism of Hcy-metabolizing enzymes in healthy adults receiving physical examination in Shanghai, China. Methods Totally 438 participants who were receiving physical examination in Shanghai Ren-ai Hospital were included in this study. The plasma total Hcy （tHcy） levels and serum folate levels were measured by enzymatic cycling methods and electrochemiluminescence, respectively. Genetic typing was determined by ligase detection reaction（LDR）. The plasma tHcy levels were compared between different genotypes, and the association of plasma tHcy levels with genetic polymorphisms was analyzed. Results The incidence of hyperhomocysteinemia （HHcy） was 28.54% （125/438） in the present study. There was significant difference in the levels of plasma tHcy among the three genotypes of MTHFR C677T （P〈0.001）.Heterozygous genotype CA of MTHFR A1298C was associated with a significantly reduced risk of HHcy （OR=0.49, 95% CI： 0.26-0.92,P=0.027）; heterozygous genotype CT of MTHFR C677T was associated with a significantly increased risk of HHcy （OR=2.15 , 95% CI： 1.06-4.36, P=0.035）, and homozygous genotype TT was also associated with a significantly increased risk of HHcy （OR=7.58, 95% CI： 3.15-18.22, P〈0.001）. No correlation was found for HHcy risk with MTR G905A, MTRR A66G, MTRR Ac.56＋781C, MTR A2756G, or CBS C551G. Conclusion TT and CT genotype of MTHFR C677T have been found to be the risks for HHcy; CA genotype of MTHFR A1298C may help to decrease the risk to HHcy.