生命脆弱年龄健康人群中15个STR座位和HLA多态性分布特点
摘要
目的:研究生命脆弱年龄健康人群中15个特定STR座位(CSF1PO、D7S820、D8S1179、D21S11、D2S1338、D3S1358、D13S317、D16S539、TH01、D18S51、D19S433、TPOX、VWA、D5S818、FGA)和HLA(HLA-A、B、DRB1)基因多态性的分布特点。
方法:选取年龄为50~70岁的健康体检者为实验组,其常规生化检测及血常规检测均正常。男女每岁各至少1例,最多4例,共计93例(男42,女51)。静脉采血(EDTA抗凝1管,分离胶促凝1管)。提取DNA,利用特异性寡核苷酸探针分析法(PCR-SSO),结合流式细胞技术进行HLA-A、B、DRB1的分型检测(实验组93例),利用毛细管电泳技术检测15个特定的STR座位(实验组50例:男24,女26)。通过三项特殊生化指标检测,验证实验组健康人群选择合理。HLA以文献资料(大连地区9678例18至45岁的骨髓干细胞志愿捐献者的HLA-A、B、DRB1位点的基因分型结果。均为汉族、身体健康的随机供者。文献资料的分型方法与本实验一致。)做对照,STR以大连地区2006年至2008年18至50岁健康、无关个体150例为对照,男女各半。比较分析两组基因位点的频率分布特点及各位点纯合子频率特点。
结果:实验组共检测到HLA特异性基因位点45个,其中,HLA-A位点10个,HLA-B位点22个,HLA-DRB1位点13个。实验组A*31的频率明显高于对照组( P<0.05),而A*11的频率明显低于对照组(P<0.05)。实验组HLA-B及HLA-DRB1基因位点的频率与对照组相比无显著性差异(P>0.05)。15个特定STR检测结果显示,实验组的D3S1358-18、D13S317-11、VWA-20、FGA-22频率明显高于对照组,两组存在显著性差异( P<0.05),而D18S51-14、FGA-20频率明显低于对照组,两组亦存在显著性差异。通过对HLA-A、B、DRB1位点及15个STR座位的纯合子频率分析,发现实验组D18S51座位各重复序列纯合子的实际频率显著低于理论频率(P<0.05)。
结论: HLA的A*31可能是有利于健康的抗病基因,A*11可能是疾病易感基因。HLA-B及HLA-DRB1各位点基因频率与疾病无明显相关性;在15个STR座位中,D3S1358-18、D13S317-11、VWA-20、FGA-22四个座位附近可能存在着抗病基因,而D18S51-14、FGA-20座位附近则可能存在着疾病易感基因。D18S51座位的杂合子表现可能有利于抵抗疾病。
Objective: To study the characteristics of distribution of genetic polymorphism in 15 specific STR loci (CSF1PO、D7S820、D8S1179、D21S11、D2S1338、D3S1358、D13S317、D16S539、TH01、D18S51、D19S433、TPOX、VWA、D5S818、FGA) and HLA (HLA-A, B and DRB1) alleles among healthy people at the age of life fragility.
Methods: Healthy people aged between 50 to 70-year old were chosen as observed group. Their regular biochemical examination and blood examination was performed and the results were in the normal range. Each section of age has at least 1 case of male or female, but its maximum number is less than four. The total number is 93. Intravenous blood sample was collected (with one tube for EDTA anticoagulation and one tube for separation gel coagulation). DNA was extracted. The typing test for HLA-A, B and DRB1 (from 93 cases in the observed group) was performed by means of PCR-SSO and FCM. Fifteen specific STR loci (from 50 cases including 24 males and 26 females in the observed group) were tested by means of capillary electrophoresis. It was verified by determination of three special biochemical indicators that the choice of healthy people in the observed group is reasonable. The following published materials were used as control for HLA: the genotyping result of loci HLA-A, B and DRB1 from 9,678 volunteer stem cell donators aged between 18 to 45 in Dalian, who were healthy random suppliers with the nationality of Chinese Han (the typing method in this experiment is same to the published papers). One hundred and fifty healthy and non-related individuals (consisting of 75 males and 75 females) aged between 18 to 50-year old in Dalian were chosen as control for STR in the period of 2006 to 2008. Characteristics of the frequency distribution of both genetic locus groups and the homozygote frequency of each locus were compared and analyzed.
Results: Fourty five specific genetic loci for HLA had been detected in the observed group, which include 10 HLA-A loci, 22 HLA-B loci and 13 HLA-DRB1 loci. The frequency of A*31 in the observed group was obviously higher than that in the control group (P<0.05). The frequency of A*11 was obviously lower than that in the control group (P<0.05). There is no significant difference between the frequency of HLA-B and HLA-DRB1 genetic loci in the observed group and the control group (P>0.05). The result of test for 15 specific STRs showed that the frequency of D3S1358-18, D13S317-11, VWA-20 and FGA-22 in the observed group was obviously higher than that in the control group and there was significant difference between the two groups (P>0.05), while the frequency of D18S51-14 and FGA-20 was obviously lower than that in the control group and there was also significant difference between these two groups. It was found out by homozygote frequency analysis of loci HLA-A, B and DRB1 and 15 STR loci that the actual frequency of each repeat homozygote of the locus D18S51 in the observed group was obviously lower than the theoretical frequency (P<0.05).
Conclusion: A*31 in HLA may be a disease-resistant gene that contributes to the health. While A*11 may be a disease-susceptible gene. The genetic frequency of loci HLA-B and HLA-DRB1 dose not have closely correlation with the disease. There may be disease-resistant genes near four loci D3S1358-18, D13S317-11, VWA-20 and FGA-22 among 15 STR loci, while there may be disease-susceptible genes near the loci D18S51-14 and FGA-20. The heterozygote at the locus D18S51 may contribute to disease resistance.
方法:选取年龄为50~70岁的健康体检者为实验组,其常规生化检测及血常规检测均正常。男女每岁各至少1例,最多4例,共计93例(男42,女51)。静脉采血(EDTA抗凝1管,分离胶促凝1管)。提取DNA,利用特异性寡核苷酸探针分析法(PCR-SSO),结合流式细胞技术进行HLA-A、B、DRB1的分型检测(实验组93例),利用毛细管电泳技术检测15个特定的STR座位(实验组50例:男24,女26)。通过三项特殊生化指标检测,验证实验组健康人群选择合理。HLA以文献资料(大连地区9678例18至45岁的骨髓干细胞志愿捐献者的HLA-A、B、DRB1位点的基因分型结果。均为汉族、身体健康的随机供者。文献资料的分型方法与本实验一致。)做对照,STR以大连地区2006年至2008年18至50岁健康、无关个体150例为对照,男女各半。比较分析两组基因位点的频率分布特点及各位点纯合子频率特点。
结果:实验组共检测到HLA特异性基因位点45个,其中,HLA-A位点10个,HLA-B位点22个,HLA-DRB1位点13个。实验组A*31的频率明显高于对照组( P<0.05),而A*11的频率明显低于对照组(P<0.05)。实验组HLA-B及HLA-DRB1基因位点的频率与对照组相比无显著性差异(P>0.05)。15个特定STR检测结果显示,实验组的D3S1358-18、D13S317-11、VWA-20、FGA-22频率明显高于对照组,两组存在显著性差异( P<0.05),而D18S51-14、FGA-20频率明显低于对照组,两组亦存在显著性差异。通过对HLA-A、B、DRB1位点及15个STR座位的纯合子频率分析,发现实验组D18S51座位各重复序列纯合子的实际频率显著低于理论频率(P<0.05)。
结论: HLA的A*31可能是有利于健康的抗病基因,A*11可能是疾病易感基因。HLA-B及HLA-DRB1各位点基因频率与疾病无明显相关性;在15个STR座位中,D3S1358-18、D13S317-11、VWA-20、FGA-22四个座位附近可能存在着抗病基因,而D18S51-14、FGA-20座位附近则可能存在着疾病易感基因。D18S51座位的杂合子表现可能有利于抵抗疾病。
Objective: To study the characteristics of distribution of genetic polymorphism in 15 specific STR loci (CSF1PO、D7S820、D8S1179、D21S11、D2S1338、D3S1358、D13S317、D16S539、TH01、D18S51、D19S433、TPOX、VWA、D5S818、FGA) and HLA (HLA-A, B and DRB1) alleles among healthy people at the age of life fragility.
Methods: Healthy people aged between 50 to 70-year old were chosen as observed group. Their regular biochemical examination and blood examination was performed and the results were in the normal range. Each section of age has at least 1 case of male or female, but its maximum number is less than four. The total number is 93. Intravenous blood sample was collected (with one tube for EDTA anticoagulation and one tube for separation gel coagulation). DNA was extracted. The typing test for HLA-A, B and DRB1 (from 93 cases in the observed group) was performed by means of PCR-SSO and FCM. Fifteen specific STR loci (from 50 cases including 24 males and 26 females in the observed group) were tested by means of capillary electrophoresis. It was verified by determination of three special biochemical indicators that the choice of healthy people in the observed group is reasonable. The following published materials were used as control for HLA: the genotyping result of loci HLA-A, B and DRB1 from 9,678 volunteer stem cell donators aged between 18 to 45 in Dalian, who were healthy random suppliers with the nationality of Chinese Han (the typing method in this experiment is same to the published papers). One hundred and fifty healthy and non-related individuals (consisting of 75 males and 75 females) aged between 18 to 50-year old in Dalian were chosen as control for STR in the period of 2006 to 2008. Characteristics of the frequency distribution of both genetic locus groups and the homozygote frequency of each locus were compared and analyzed.
Results: Fourty five specific genetic loci for HLA had been detected in the observed group, which include 10 HLA-A loci, 22 HLA-B loci and 13 HLA-DRB1 loci. The frequency of A*31 in the observed group was obviously higher than that in the control group (P<0.05). The frequency of A*11 was obviously lower than that in the control group (P<0.05). There is no significant difference between the frequency of HLA-B and HLA-DRB1 genetic loci in the observed group and the control group (P>0.05). The result of test for 15 specific STRs showed that the frequency of D3S1358-18, D13S317-11, VWA-20 and FGA-22 in the observed group was obviously higher than that in the control group and there was significant difference between the two groups (P>0.05), while the frequency of D18S51-14 and FGA-20 was obviously lower than that in the control group and there was also significant difference between these two groups. It was found out by homozygote frequency analysis of loci HLA-A, B and DRB1 and 15 STR loci that the actual frequency of each repeat homozygote of the locus D18S51 in the observed group was obviously lower than the theoretical frequency (P<0.05).
Conclusion: A*31 in HLA may be a disease-resistant gene that contributes to the health. While A*11 may be a disease-susceptible gene. The genetic frequency of loci HLA-B and HLA-DRB1 dose not have closely correlation with the disease. There may be disease-resistant genes near four loci D3S1358-18, D13S317-11, VWA-20 and FGA-22 among 15 STR loci, while there may be disease-susceptible genes near the loci D18S51-14 and FGA-20. The heterozygote at the locus D18S51 may contribute to disease resistance.
引文
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1.刘辉.长寿研究中长寿人群和对照组的确定.中国老年学杂志, 2007,27(7):678-679
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6. Lagaay AM, D'Amaro J, Ligthart GJ, Schreuder GM, van Rood JJ, Hijmans W. Longevity and heredity in humans. Association with the human leucocyte antigen phenotype. Ann N Y Acad Sci. 1991;621:78-89.
7. De Benedictis G, Carotenuto L, Carrieri G, Luca MD, Falcone E, Rose G, Cavalcanti S, Corsonello F, Feraco E, Baggio G, Bertolini S, Mari D, Mattace R, Yashin AI, BonafèM, Franceschi C Gene/longevity association studies at four autosomal loci (REN, THO, PARP,SOD2). Eur J Hum Genet 1998; 6(6): 534-541
8.孟庆丽、于卫建等.辽南地区造血干细胞捐献者HLA基因发布和单倍型分析.中国输血杂志,2007,20(1):30-32
9. Buyse I, Sandkuyl LA., Zamani Ghabanbasani M, Gu XX, Bouillon R., Bex M., Dooms L, Emonds MP, Duhamel M, Marynen P, et al. Association of particular HLA class II alleles, haplotypes and genotypes with susceptibility to IDDM in the Belgian population. Diabetologia, 37, 808-817
10. Sch?chter F, Faure-Delanef L, Guénot F, et al. Genetic associations with longevity at the APOE and ACE loci. Nature Genet, 1994, 6,29–32
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12. Mari D, Mannucci PM, Duca F, et al. Mutant factor V (Arg506Gln) in healthy centenarians. Lancet, 1996, 347, 1044
13. Ricci G, Colombo C, Ghiazza B, et al. Association between longevity and allelic forms of human leukocyte antigens (HLA): population study of aged Italian human subjects. Arch Immunol Ther Exp (Warsz). 1998, 46(1):31-4
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18.郝宏蕾,吴微微等.浙江汉族人群15个STR基因座遗传多态性.中国法医学杂志,2006,21(5):303-304
19.杨玉玲,王冬花等.安徽汉族人群人群15个STR基因座遗传多态性.中国法医学杂志,2007,23(1):36-38
20.高雅,李生斌. STR遗传多态性研究中样本数量对等位基因检出数量的影响.遗传,2008,30(3):313-320