中文摘要：

目的：探讨NKX2—5基因与先天性心脏病（congenital heart disease，CHD）的关系。方法：收集130例无血缘关系的CHD患者的临床资料和血标本，以100名无血缘关系的健康者为对照。应用聚合酶链反应扩增CHD候选基因NKX2—5的全部外显子和外显子两侧的部分内含子，采用双脱氧核苷链末端合成终止法对全部扩增片段进行测序。将所测的序列与GenBank数据库中公布的NKX2—5基因序列进行比对以识别出NKX2—5基因变异。比较识别出的NKX2—5基因多态在CHD患者和健康对照者间的频率分布差异。结果：在CHD患者的NKX2—5基因识别出2个单核苷酸多态，一个是NKx2—5基因编码序列第63位的腺嘌呤（A）变为鸟嘌呤（G），即c．63A〉G多态；另一个是NKx2—5基因编码序列第606位的G变为胞嘧啶（C），即c．606G〉C多态。在NKX2—5基因第606位点的等位基因G、C及其构成的3种基因型GG、GC、CC在CHD患者和健康对照者间的频率分布有显著性差异（等位基因频率比较：X^2=4．125，P=0．042；基因型频率比较：X^2=4．279，P=0．039）。但在NKX2—5基因第63位点的等位基因A、G及其构成的3种基因型AA、AG、GG在CHD患者和健康对照者间的频率分布无显著性差异（等位基因频率比较：X^2=0．704，P=0．402；基因型频率比较：X^2=0．626，P=0．429）。结论：NKX2—5基因c．606G〉C多态可能与CHD有关，等位基因606C携带者可能对CHD的易感性增加。

英文摘要：

Objective：To explore the association of the NKX2-5 gene with congenital heart disease （CHD）. Methods..A cohort of 130 unrelated subjects with CHD and a total of 100 unrelated healthy individuals as controls were registered. The clinical data were recorded and the peripheral venous blood specimens were prepared. The complete exons and flanking partial introns of the candidate gene NKX2-5 were amplified by polymerase chain reaction and the amplicons were sequenced using the di-deoxynucleotide chain termination procedure. The acquired sequences were aligned with those of NKX2-5 publicized in GenBank by the aid of programme BLAST to identify the sequence variations. The difference of polymorphic frequency distributions between CHD patients and controls was tested by Chi-square test where a two-tailed P〈0.05 was considered statistically significant. Results：Two single nucleotide potymorphisms of the NKX2-5 gene were identified in CHD patients. One is the substitution of guanine （G） for adenine （A） at nucleotide 63 of the eoding sequence of the NKX2-5 gene （c. 63A〉G）, and the other is the transition of G into cytosine （C） at nucleotide 606 （c. 606G〉C）. The prevalence of the allelie G and C, and the genotypes GG, GC, and CC at nucleotide 606 in CHD patients was statistically different from that in healthy controls （for alleles, ;（2 = 4. 125,P = 0. 042 ; for genotypes, X^2 = 4. 279, P = 0. 039）. However, the polymorphic frequency distribution of c. 63A〉G in CHD cases was not statistically different from that in healthy controls （for alleles, X^2 = 0.704, P = 0. 402 ; for genotypes, X^2 = 0. 626, P = 0. 429）. Conclusion： These findings suggest that the single nucleotide polymorphism, c. 606G〉C, of the NKX2-5 gene may be related to CHD and the individuals carrying the allele 606C may be associated with increased susceptibility to CHD.