【作者】 刘丙立；

【导师】 李子荣；

【作者基本信息】 中国协和医科大学 ， 外科学， 2010， 博士

【摘要】 目的非创伤性股骨头坏死病因不明,目前国外已有相关报道股骨头坏死与基因变异相关,但国内尚未开展,本研究从DAN的角度探索非创伤性股骨头坏死的易感基因,筛查与股骨头坏死相关的SNP。方法自2007-1至2009-6收集非创伤性股骨头坏死患者243例,男156例,女87例,年龄范围16-64岁,根据病史分为激素性143例,酒精性79例,特发性21例。选择与病例组患者年龄,性别及民族相匹配正常人96例作为对照组。对所有受试者收集血液标本进行肝脂肪酶启动子部分区域的DNA测序,包括脂联素两个常见SNP在内的部分DNA序列,及包括亚甲基四氢叶酸脱氢酶(MTHFR)两个常见SNP位点在内的部分DNA序列。找出所测序列中出现SNP的,统计其基因型及等位基因频率,并进行“病例-对照”分析,分析其与股骨头坏死的相关性。结果1在MTHFR所测区域发现rs1801133,rs1801131两个SNP,病例对照分析发现两个SNP与酒精性股骨头坏死存在相关性。其中rs1801133中T等位基因在酒精性骨坏死组中出现率更高。而rs1801131的A等位基因及AA基因型在酒精性骨坏死组中出现率更高。2在脂联素所测区域发现rs2241766, rs61322123两个SNP,但病例对照分析发现两SNP与非创伤性股骨头坏死均无相关性。3在肝脂肪酶所测区域发现rs59644784,rs1800588两个SNP,但病例对照分析发现两个SNP与非创伤性股骨头坏死均无相关性。结论1MTHFR基因中rs1801131, rs1801133两个SNP均与酒精性股骨头坏死相关。2脂连素基因中rs2241766, rs61322123杂合度较高,两者均与非创伤性股骨头坏死无统计学相关性。3肝脂肪酶基因中rs59644784, rs1800588两个SNP杂合度较高,但两者均与非创伤性股骨头坏死无相关性。4非创伤性股骨头坏死与某些DNA序列的改变相关。更多还原

【Abstract】 Objective The etiological factor of the non-traumatic osteonecrosis of femoral head were not clear. It have some reports about relation between the gene and the non-traumatic osteonecrosis of femoral head in other country.but it have not the report about it. This study to explore the susceptibility genes of nontraumatic femoral head necrosis from the perspective of DNA, to screen the SNP associated with non-traumatic osteonecrosis of femoral head. Methods From 2007-1 to 2009-6,243 cases with nontraumatic osteonecrosis of femoral head were collected, male 156 cases, female 87 cases, age range 16 to 64 years, according to the history of the disease,143 cases were divided into glucocorticoids group,79 cases alcohol group,21 cases idiopathic group. Select 96 normal subjects matched with patients age, sex and ethnic as control group. Blood samples were collected on all subjects.To Sequence the DNA sequencing that include the hepatic lipase promoter region, the region including two common SNP of adiponectin, the region including two common SNP of methylenetetrahydrofolate dehydrogenase (MTHFR). To identify the high heterozygosity SNP and to statistic of their genotype and allele frequencies, the results were analysed according to case-control principle. Results 1 We found rs1801133,rs1801131 two SNPs in the sequenced region of MTHFR. The two SNPs associated with alcohol-induced osteonecrosis of femoral head. The probability of T allele of rs1801133 in the group of alcohol-induced osteonecrosis was higher. The probability of A-allele and AA genotype of rs1801131 in alcohol-induced osteonecrosis group was higher.2 The sequenced region of adiponectin found rs2241766, rs61322123 two SNPs, but the correlation with non-traumatic osteonecrosis of femoral head were not found.3 The hepatic lipase promoter region found rs59644784, rs1800588 two SNPs, but the correlation with non-traumatic osteonecrosis of femoral head were not found. Conclusion 1 The rs1801131, rs1801133 in MTHFR gene both were associated with the alcohol-induced osteonecrosis of femoral head.2 The heterozygosity of rs2241766, rs61322123 in adiponectin gene were higher, but they had not the correlation with non-traumatic osteonecrosis of femoral head 3 The heterozygosity of rs59644784, rs1800588 in hepatic lipase gene were higher, but they had not the correlation with non-traumatic osteonecrosis of femoral head.4 non-traumatic femoral head necrosis may be related to certain changes in DNA sequence.更多还原