Cystatin C基因5’端-157G/C突变与老年性痴呆的相关性研究
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摘要
第一部分 Cystatin C基因5’端-157G/C突变与老年性痴呆的相关性研究
目的 探讨Cystatin C基因5’端-157G/C突变与中国昆明地区汉族人老年性痴呆是否存在关联。方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法在134例无亲缘关系之中国昆明汉族人(正常对照者73例,老年性痴呆患者61例)中对Cystatin C基因变异进行检测。同时检测两组人群血浆Cystatin C之浓度。结果 在老年性痴呆患者中GG、GC和CC基因型频率分别为16.4%、50.8%和32.8%;正常对照者组中分别为26.0%、41.1%和32.9%。G等位基因频率在老年性痴呆组中和正常对照者组中分别为41.8%和46.6%。基因型频率和等位基因频率在两组之间无统计学差异。两组人群血浆Cystatin C浓度也无统计学差异。结论 在中国昆明汉族人群中存在Cystatin C基因5’端-157G/C变异的多态性,但可能对老年性痴呆的发生不起主要作用。
Objective To investigate the correlation between the G/C variant at -157 position of the Cystatin C gene 5' flanking region and Alzheimer's disease in Kunming Chinese subjects. Methods One hundred and thirty-four unrelated Kunming Han Chinese subjects (seventy-three control subjects and sixty-one patients with Alzheimer's disease)were studied by polymerase chain reaction-restriction fragment length polymorphism assay. And determine the concentration of Cystatin C in patients with AD and in control subjects .Results Genotype frequency of GG, GC and CC was16. 4%, 50. 8%和32. 8% in patients with AD and 26. 0%, 41. 1%和32. 9% in control subjects. The G allele frequency was 41.8% in patients with AD and 46.6% in control subjects. There was no statistical difference either in genotype or in allele frequency between patients with AD and control subjects. There was no statistical difference in concentration of Cystatin C between patients with AD and control subjects. Conclusion The G/C variant at -157 position of the Cystatin C gene 5' flanking region exists in Yunnan Kunming Chinese and this variant dose not play a major role in the on set of Alzheimer's disease.
目的 探讨Cystatin C基因5’端-157G/C突变与中国昆明地区汉族人老年性痴呆是否存在关联。方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法在134例无亲缘关系之中国昆明汉族人(正常对照者73例,老年性痴呆患者61例)中对Cystatin C基因变异进行检测。同时检测两组人群血浆Cystatin C之浓度。结果 在老年性痴呆患者中GG、GC和CC基因型频率分别为16.4%、50.8%和32.8%;正常对照者组中分别为26.0%、41.1%和32.9%。G等位基因频率在老年性痴呆组中和正常对照者组中分别为41.8%和46.6%。基因型频率和等位基因频率在两组之间无统计学差异。两组人群血浆Cystatin C浓度也无统计学差异。结论 在中国昆明汉族人群中存在Cystatin C基因5’端-157G/C变异的多态性,但可能对老年性痴呆的发生不起主要作用。
Objective To investigate the correlation between the G/C variant at -157 position of the Cystatin C gene 5' flanking region and Alzheimer's disease in Kunming Chinese subjects. Methods One hundred and thirty-four unrelated Kunming Han Chinese subjects (seventy-three control subjects and sixty-one patients with Alzheimer's disease)were studied by polymerase chain reaction-restriction fragment length polymorphism assay. And determine the concentration of Cystatin C in patients with AD and in control subjects .Results Genotype frequency of GG, GC and CC was16. 4%, 50. 8%和32. 8% in patients with AD and 26. 0%, 41. 1%和32. 9% in control subjects. The G allele frequency was 41.8% in patients with AD and 46.6% in control subjects. There was no statistical difference either in genotype or in allele frequency between patients with AD and control subjects. There was no statistical difference in concentration of Cystatin C between patients with AD and control subjects. Conclusion The G/C variant at -157 position of the Cystatin C gene 5' flanking region exists in Yunnan Kunming Chinese and this variant dose not play a major role in the on set of Alzheimer's disease.
引文
[1] 盛树力主编。老年性痴呆:从分子生物学到临床诊治。科学技术文献出版社。1998。
[2] Marin DB, Breuer B, Marin ML, et al. The relationship between apoliporotein E, dementia, and vascular illness. Atherosclerosis 1998; 140:173-180.
[3] Ji Y, Urakami K, Adachi Y, et al. Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease. Dement Geriatr Cogn Disord 1998;243-245.
[4] Premkumar DR, Cohen DL, Hedera P, et al. Apolipoprotein E-epsilon 4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol 1996;148:2083-2095.
[5] Treves TA, Bornstein NM, Chapman J, et al. APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1996;10:189-191.
[6] Isoe K, Urakami K, Sato K, et al. Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia. Acta Neurol Scand 1996;93:133-137.
[7] Paskalev E, Lambreva L, Simeonov P, et al. Serum Cystatin C in renal transplant patients[J]. Clinica chimica Acta 2001; 310(1): 53-56.
[8] Henskens YM, Veerman EC, Nieuw Amerongen AV. Cystatins in health and disease. Biol Chem Hoppe Seyler 1996;377:71-86.
[9] Skoog I, Kalaria RN, Breteler MM. Vascular factors and Alzheimer disease. Alzheimer Dis Assoc Disord 1999;13(suppl. 3):S106-S114.
[10] Schmidt R, Schmidt H, Fazekas F. Vascular risk factors in dementia. J Neurol 2000;247:81-87.
[11] Sparks DL. Coronary artery disease, hyoertension APOE, and cholesterol :a link to Alzheimer's disease? Ann NY Acad Sci 1997;8d26:128-146.
[12] Boston PF, Dennis MS, Jagger C. Factors associated with vascular dementia in an elderly community population. Imt H Geriatr Psychiatry 1999;14:761-766.
[13] Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997;42:776-782.
[14] Levy E, Lopez-Otin C, Ghiso J, et al. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med 1989; 169:1771-1778.
[15] Jensson O, Gudmundsson G, Arnason A, et al. Hereditary cystatin C (gamma-tree) amyloid angiopathy of the CNS causing cerebral hemorrhage. Acta Neurol Scand 1987;76:102-114.
[16] Roks G, Cruts M, Slooter AJC, et al. The cystatin C polymorphism is not associated with early onset Alzheimer's disease. Neurology 2001;57(2): 366-367.
[17] MaruyamaH, Izumi Y, Oda M, et al. Lack of an association between cystatin C gene polymorphisms in Japanese patients with Alzheimer's disease. Neurology 2001;57(2):337-339.
[18] Crawford FC, Freeman MJ, Schinka JA, et al. A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease. Neurology 2000;55(2):763-768.
[19] Dodel RC, Du Y, Depboylu C, et al. A polymorphism in the cystatin C promoter region is not associated with an increased rise of AD. Neurology 2002;58(2) :664.
[20] 中华医学会精神科分会主编。中国精神障碍分类与诊断标准第三版。山东科学技术出版社。2001年4月,第一版。
[21] Balbin M, Abrahamson M. Sst Ⅱ polymorphic sites in the promoter region of the human cystatin C gene. Hum Genet 1991;87:751-752.
[22] 段勇,王玉明,赵淮,等。从血细胞快速提取DNA的方法探讨。昆明医学院学报,1998;19(2):28。
[23] P.C.温特,G.L.希基,H.L.弗莱彻。遗传学。科学出版社。2001:208-215。
[24] Ying GX, Huang C, Jiang ZH, et al. Up-gluation of cystatin c expression in the murine hippocampus following perfornt path transactions[J]. Neuroscience 2002; 112(12): 289-298.
[25] Finney H, Newman DJ, Gruber W, et al. Initial evaluation of cystatin C measurement by partice-enchanced immunonephlometry on the Behring Nephelometer systems(BNA, BN Ⅱ) [J]. Clin Chem 1997; 43(6 pt 1): 1016-1022.
[26] Thorsteinsson L, Georgssson G, Asgeirsson B, et al. On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy. J Neurol Sci 1992;108:121-128.
[27] Bjarnadottir M, Wulti BS, Sameni M, et al. Inteaceliular accumulation of the amyloidogenic L68Q variant of human cystatinC in NIH/3T3 cells. Mol Pathol 1998;51:317-326.
[28] Benedikz E, Merz GS, Schwenk V, et al. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type. Amyloid 1999;6:172-182.
[29] Wang ZZ, Jensson O, Thorsteinsson I, et al. Microvascular degeneration in hereditary cystatin C amyloid angiopathy of the brain. APHIS 1997;105:41-47.
[30] Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease:the CERAD experience,Part XV. Neurology 1996;46:1592-1596.
[31] Vinters HV, Nishimura GS, Sedor DL, et al. Immunoreactive A4 and gamma-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with Alzheimer's disease. Am J Pathol 1990;137:233-240.
[2] Marin DB, Breuer B, Marin ML, et al. The relationship between apoliporotein E, dementia, and vascular illness. Atherosclerosis 1998; 140:173-180.
[3] Ji Y, Urakami K, Adachi Y, et al. Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease. Dement Geriatr Cogn Disord 1998;243-245.
[4] Premkumar DR, Cohen DL, Hedera P, et al. Apolipoprotein E-epsilon 4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol 1996;148:2083-2095.
[5] Treves TA, Bornstein NM, Chapman J, et al. APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1996;10:189-191.
[6] Isoe K, Urakami K, Sato K, et al. Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia. Acta Neurol Scand 1996;93:133-137.
[7] Paskalev E, Lambreva L, Simeonov P, et al. Serum Cystatin C in renal transplant patients[J]. Clinica chimica Acta 2001; 310(1): 53-56.
[8] Henskens YM, Veerman EC, Nieuw Amerongen AV. Cystatins in health and disease. Biol Chem Hoppe Seyler 1996;377:71-86.
[9] Skoog I, Kalaria RN, Breteler MM. Vascular factors and Alzheimer disease. Alzheimer Dis Assoc Disord 1999;13(suppl. 3):S106-S114.
[10] Schmidt R, Schmidt H, Fazekas F. Vascular risk factors in dementia. J Neurol 2000;247:81-87.
[11] Sparks DL. Coronary artery disease, hyoertension APOE, and cholesterol :a link to Alzheimer's disease? Ann NY Acad Sci 1997;8d26:128-146.
[12] Boston PF, Dennis MS, Jagger C. Factors associated with vascular dementia in an elderly community population. Imt H Geriatr Psychiatry 1999;14:761-766.
[13] Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997;42:776-782.
[14] Levy E, Lopez-Otin C, Ghiso J, et al. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med 1989; 169:1771-1778.
[15] Jensson O, Gudmundsson G, Arnason A, et al. Hereditary cystatin C (gamma-tree) amyloid angiopathy of the CNS causing cerebral hemorrhage. Acta Neurol Scand 1987;76:102-114.
[16] Roks G, Cruts M, Slooter AJC, et al. The cystatin C polymorphism is not associated with early onset Alzheimer's disease. Neurology 2001;57(2): 366-367.
[17] MaruyamaH, Izumi Y, Oda M, et al. Lack of an association between cystatin C gene polymorphisms in Japanese patients with Alzheimer's disease. Neurology 2001;57(2):337-339.
[18] Crawford FC, Freeman MJ, Schinka JA, et al. A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease. Neurology 2000;55(2):763-768.
[19] Dodel RC, Du Y, Depboylu C, et al. A polymorphism in the cystatin C promoter region is not associated with an increased rise of AD. Neurology 2002;58(2) :664.
[20] 中华医学会精神科分会主编。中国精神障碍分类与诊断标准第三版。山东科学技术出版社。2001年4月,第一版。
[21] Balbin M, Abrahamson M. Sst Ⅱ polymorphic sites in the promoter region of the human cystatin C gene. Hum Genet 1991;87:751-752.
[22] 段勇,王玉明,赵淮,等。从血细胞快速提取DNA的方法探讨。昆明医学院学报,1998;19(2):28。
[23] P.C.温特,G.L.希基,H.L.弗莱彻。遗传学。科学出版社。2001:208-215。
[24] Ying GX, Huang C, Jiang ZH, et al. Up-gluation of cystatin c expression in the murine hippocampus following perfornt path transactions[J]. Neuroscience 2002; 112(12): 289-298.
[25] Finney H, Newman DJ, Gruber W, et al. Initial evaluation of cystatin C measurement by partice-enchanced immunonephlometry on the Behring Nephelometer systems(BNA, BN Ⅱ) [J]. Clin Chem 1997; 43(6 pt 1): 1016-1022.
[26] Thorsteinsson L, Georgssson G, Asgeirsson B, et al. On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy. J Neurol Sci 1992;108:121-128.
[27] Bjarnadottir M, Wulti BS, Sameni M, et al. Inteaceliular accumulation of the amyloidogenic L68Q variant of human cystatinC in NIH/3T3 cells. Mol Pathol 1998;51:317-326.
[28] Benedikz E, Merz GS, Schwenk V, et al. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type. Amyloid 1999;6:172-182.
[29] Wang ZZ, Jensson O, Thorsteinsson I, et al. Microvascular degeneration in hereditary cystatin C amyloid angiopathy of the brain. APHIS 1997;105:41-47.
[30] Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease:the CERAD experience,Part XV. Neurology 1996;46:1592-1596.
[31] Vinters HV, Nishimura GS, Sedor DL, et al. Immunoreactive A4 and gamma-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with Alzheimer's disease. Am J Pathol 1990;137:233-240.