CAJ | 학술논문

目的：研究新疆哈萨克族人群中扩张型心肌病（DCM）与核纤层蛋白A（LMNA）基因变异的关系。 　　方法：对哈萨克族一个家族性扩张型心肌病（FDCM）31名成员，特发性扩张型心肌病（IDCM）160例患者（哈萨克族80例、汉族80例）分为IDCM组（哈萨克族,简称哈）、IDCM组（汉族,简称汉）及160例健康志愿者（哈萨克族80例、汉族80例）分为对照组（哈）、对照组（汉）进行LMNA基因检测。提取外周血DNA，聚合酶链反应（PCR）扩增LMNA基因的12个外显子和外显子附近的内含子，对目的基因进行测序，测序结果与CHROMAS软件和PUBMED中BLAST软件中的标准模板进行对比，并分析突变位点与哈萨克族IDCM和汉族IDCM之间的关系。 　　结果：在哈萨克族FDCM的先证者中检测到LMNA基因7号外显子一未报道的单个碱基C插入（insC, CGG→CCG），导致精氨酸（Arg）变为脯氨酸（Pro）。在10号外显子上，检测到一个已被报道的LMNA基因多态位点rs4641（c.1362C>T, His454His）。随后，在IDCM组（哈）和其对照组的LMNA基因检测结果中，得出LMNA基因多态位点rs4641的基因型分布（χ2=5.16，P=0.036）和等位基因频率（χ2=4.50，P=0.034）均存在统计学意义，而在IDCM组（汉）和其对照组中却差异无统计学意义。Logistic回归分析显示LMNA基因rs4641多态位点与IDCM组（哈）存在相关性[P=0.025，比值比（OR）=0.412，95%可信区间（CI）：0.189~0.896]。 　　结论：LMNA基因在新疆汉族和哈萨克族均有较高的患病率，但经统计后，发现LMNA基因rs4641多态位点与新疆地区哈萨克族DCM存在关联，可能是新疆地区DCM患者发病的易感基因多态位点。
목적：연구신강합살극족인군중확장형심기병（DCM）여핵섬층단백A（LMNA）기인변이적관계。 　　방법：대합살극족일개가족성확장형심기병（FDCM）31명성원，특발성확장형심기병（IDCM）160례환자（합살극족80례、한족80례）분위IDCM조（합살극족,간칭합）、IDCM조（한족,간칭한）급160례건강지원자（합살극족80례、한족80례）분위대조조（합）、대조조（한）진행LMNA기인검측。제취외주혈DNA，취합매련반응（PCR）확증LMNA기인적12개외현자화외현자부근적내함자，대목적기인진행측서，측서결과여CHROMAS연건화PUBMED중BLAST연건중적표준모판진행대비，병분석돌변위점여합살극족IDCM화한족IDCM지간적관계。 　　결과：재합살극족FDCM적선증자중검측도LMNA기인7호외현자일미보도적단개감기C삽입（insC, CGG→CCG），도치정안산（Arg）변위포안산（Pro）。재10호외현자상，검측도일개이피보도적LMNA기인다태위점rs4641（c.1362C>T, His454His）。수후，재IDCM조（합）화기대조조적LMNA기인검측결과중，득출LMNA기인다태위점rs4641적기인형분포（χ2=5.16，P=0.036）화등위기인빈솔（χ2=4.50，P=0.034）균존재통계학의의，이재IDCM조（한）화기대조조중각차이무통계학의의。Logistic회귀분석현시LMNA기인rs4641다태위점여IDCM조（합）존재상관성[P=0.025，비치비（OR）=0.412，95%가신구간（CI）：0.189~0.896]。 　　결론：LMNA기인재신강한족화합살극족균유교고적환병솔，단경통계후，발현LMNA기인rs4641다태위점여신강지구합살극족DCM존재관련，가능시신강지구DCM환자발병적역감기인다태위점。
Objective: To study the relationship between dilated cardiomyopathy and nuclear lamina protein (LMNA) gene mutation in Kazak ethnics at Xinjiang area. Methods: A Kazak familial dilated cardiomyopathy (FDCM) with 31 members was studied. In addition, 160 patients with idiopathic dilated cardiomyopathy (IDCM) with 160 healthy controls were enrolled in our study, and they were divided into 4 groups: IDCM-Kazak, IDCM-Han and Control-Kazak, Control-Han.n=80 in each group. Peripheral blood DNA were extracted, 12 exons with nearby introns of LMNA gene were detected by PCR and the ampliifed products were sequenced and compared with the standard template of CHROMAS and BLAST software to identify mutation sites. LMNA mutation in both Kazak and Han IDCM patients were investigated. Results: A novel LMNA mutation (insC, CGG→CCG) at exon 7 was identiifed in a FDCM proband, it caused an amino acid substitution as Arg to Pro, and a known LMNA polymorphism loci rs4641 (c.1362C>T His454His) was fund at exon 10. In addition, LMNA polymorphism loci rs4641 genotype distribution (χ2=5.16,P=0.036) and allele frequency (χ2=4.50,P=0.034) were statistically different between IDCM-Kazak group and Control-Kazak group; while such differences were no statistic meaning between IDCM-Han group and Control-Han group. Logistic regression analysis indicated that LMNA polymorphism loci rs4641 was related to IDCM occurrence in Kazak ethnics (P=0.025, OR=0.412, 95% CI 0.189-0.896). Conclusion: LMNA polymorphism loci rs4641 was related to IDCM in Kazak ethnics at Xinjiang area, which might be susceptible loci for IDCM occurrence.