ACE基因插入/缺失及β_2肾上腺素受体基因多态性与房颤的相关性研究

Study of association of polymorphism in angiotensin-concerting enzyme insertion/deletion gene and β2-adrenergic receptor 16 locus genes with atrial fibrillation

目的：研究血管紧张素转换酶基因插入／缺失（ACEI／D）多态性及隧肾上腺素受体基因（β2-AR＋46A—G）多态性与心房颤动的相关性，寻找房颤发病的分子机制。方法：选择55例房颤患者（房颤组）及63例非房颤者（对照组），用PCR的方法检测两组ACE基因插入／缺失多态性，用RFLP法检测隧-AR＋46A→G变异。结果：房颤组与对照组ACEI／D多态性缺失纯合型（DD型）、杂合子（DI型）、插入纯合型（Ⅱ）基因型频率分别为32．76％、41．8％、25．5％和19．0％、44．4％、36．5％；房颤组与对照组β2-AR＋46A→G多态性Gly16纯合型、Arg16纯合型、Gly16／Arg16基因型频率分别是12．7％、17．47％、61．8％和14．3％、25．3％、60．3％；房颤组与对照组D等位基因、I等位基因分布频率为53．6％、46．4％和41．2％、58．7％；房颤组与对照组Gly16等位基因、Arg16等位基因分布频率为39．6％、60．4％和38．9％、61．1％；其中D等位基因分布频率在房颤组中较对照组明显增大；在9种不同基因型联合中发现，Gly／Arg型＋DD型和Gly型＋DD型的两种联合在房颤组和对照组间的分布有明显差异（P〈0．05），且这两种联合基因型发病相对危险度（OR）=2．455（95％CI：1．080～5．579）。结论：D等位基因可能是房颤的易患因素；ACEDD基因型与心肌纤维化及心脏重构的关系较为紧密，β2-AR基因＋46A→G多态性、ID基因型和Ⅱ基因型与心肌纤维化及心脏重构无明显相关性；β2-ARGly16等位基因与ACEDD基因型的联合可能对房颤的患病有着潜在的影响。

Objective：To study the association of polymorphism in the angiotensin - concerting enzyme （ACE） insertion/deletion （I/D） gene and β2- adrenergic receptor 16 locus genes of Han people with atrial fibrillation （AF） in southwest China and the effects of gene polymorphisms on the structural remodeling of atrial myocardiurn in order to explore the molecular biological genesis of atrial fibrillation. Methods; 118 unrelated Han subjects including 55 AF subjects and 63 non - AF ones were selected from our hospital. Their genotypes of ACE （I/D） gene and β2- AR16 locus gene were identified by polymemse chain reaction （PCR） and PCR - restricted fragment length polyrnorphism assay （RFLP - PCR）. Result：The frequency of the DD, ID, Ih allele D, allele I genotype of ACE in AF group and control group was 32. 76%, 41.8%, 25. 5%, 53. 6%, 46. 4% and 19. 0%, 44. 4%, 36. 5%, 41. 2%, 58. 70/00, respectively. The frequency of the Gly16 homozygotes, Arg16 honozygotes, Gly16/ Arg16, allele Gly16, allele Arg16 genotype of β2 AR16 locus gene in AF group and control group was 12. 7%, 17. 47%, 61.8%, 39. 6%, 60. 4% and 14. 3%, 25. 3%, 60. 3%, 38. 954, 61. 1M, respectively. After the two kinds of genotypes were combined,it was found that the distribution of combination of DD genotype with allele Gly16 had significant difference between AF group and control group. Conclusions： The polyrnorphism of ACE （I/D） gene and β2-adrenergic receptor 16 locus gene are not associated with AF, but the allele D may be the risk factor for ATT The DD genotype of ACE may have significant relationship with the structural remodeling of atrial myocardiunx The polyrnorphism of the β2- AR16 locus genes, DI genotype and II genotype are also no associated with AF. Maybe there is a potential synergistic effect between DD genotype and allele Gly16 on AF.