动脉粥样硬化遗传易感性与HUMARA（GGC）n基因多态性的相关性研究

目的 :研究雄激素受体基因 （HU MARA ）多态性在陕西地区老年动脉粥样硬化 （AS）人群中分布规律及其该位点与 AS遗传易感性的关系。方法 :应用 PCR- Am p- FL P（多聚酶链反应扩增片段长度多态性 ）技术对老年 AS患者 10 0例及非 AS老年人 78例 HU MARA - STR（短串联重复序列 short tandem repeats）位点进行多态性分析。结果 :在正常人群中 HU MARA基因 GGC位点共检测出 16种基因型 ,13个等位基因 ,其片段大小在 177～ 2 6 7bp,杂合度为 85 %,多态信息量 （polymorphism information content,PIC）为 0 .80 ;AS人群 HU MARA基因 GGC位点共检出 15种基因型 ,13个等位基因 ,其片段大小为 195～ 2 37bp,杂合度为 77%,多态信息量为 0 .72 ,两群体中基因频率分布有显著差异 （P<0 .0 1） ,发现某些片段存在基因频率分布高峰 ,在两群体中亦有差异性。结论 :推测 HU -MARA基因 STR多态位点与 AS的遗传易感性相关。     

遵义汉族人群维生素D受体基因FokⅠ多态性与强直性脊柱炎的关系

目的 探讨遵义汉族人群维生素D受体（VDR）基因第二外显子（Fok Ⅰ位点）多态性与强直性脊柱炎（AS）的关系.方法 收集遵义地区汉族人群静脉血标本110例,其中AS患者49例（AS组）,体检健康者61例（对照组）;采用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）法测定两组标本的VDR基因Fok Ⅰ酶切位点多态性,观察AS组和对照组中基因型频率和基因频率分布规律,分析其与AS的关系.结果 AS组中Fok Ⅰ的等位基因频率F为74.00％、f为26.00％,对照组中分布F为73.80％、f为26.20％;两组中基因型分布比较,P均＞0.05.结论 VDR基因Fok Ⅰ酶切位点多态性与遵义汉族人群的AS发病无关.     

老年动脉粥样硬化患者雄激素受体基因多态性的分布及临床意义

目的　研究雄激素受体基因多态性在老年人动脉粥样硬化 (AS)中的分布规律及该位点与AS的关系。　方法　应用多聚酶链反应扩增片段长度多态性 (PCR Amp FLP)技术对 10 0例老年AS患者及 78例非AS患者雄激素受体基因位点短串联重复序列 (STR)进行多态性分析。　结果　在该位点重复单位为GGC ,片段大小在 177～ 2 6 7bp之间 ,重复次数为 9～ 39次 ,杂合度为 85 % ,多态信息量 (PIC)为 0 80 ;AS患者中雄激素受体基因位点片段大小在 195～ 2 37bp之间 ,重复次数为15～ 2 9次 ,杂合度为 77% ,PIC为 0 72 ,两组的基因频率分布差异有显著性 (P <0 0 0 1) ;男性、女性的AS组与对照组比较差异均有显著性 (P <0 0 5 ) ;非AS组男性与女性比较差异无显著性 (P >0 0 5 ) ;AS组男性与女性比较差异有显著性 (P <0 0 5 )。　结论　雄激素受体基因GGC位点改变可能对不同性别 ,尤其是老年男性易患AS具有一定的作用 ,该位点可能可以作为老年人AS一种遗传标记。     

内皮细胞型一氧化氮合酶基因多态性与糖尿病肾病的相关性研究

目的：探讨内皮细胞型一氧化氮合酶（eNOS)基因第7外显子894G→T点突变,及其第4内含子的1个27bp的插入／缺失（a/b)多态性,与2型糖尿病肾病（DN）之间的关系。方法：894G→T点突变采用聚合酶链反应限制性片段长度多态性（PCR－RFLP）技术,27bp的a/b多态性采用聚合酶链反应结合4％琼脂糖凝胶电泳分离技术。比较各组间的等位基因频率与基因型频率。结果：（1）早期糖尿病肾病组（DN^ 组）T等位基因及TG基因型频率显著高于糖尿病非肾病患者（DN^-组,P＜0．05）。（2）DN^ 组a等位基因及ab基因型频率显著高于DN^-组（P＜0．05）。（3）DN^ 组的TGab基因型频率亦显著高于DN^-组（P＜0．05）。（4）糖基化血红蛋白（GHbA1c),收缩压（SBP）,总胆固醇（TC）,eNOS基因第7外显子894G→T基因点突变及第4内含子a/b多态性均属糖尿病肾病的独立危险因素。结论：糖尿病患者eNOS基因第7外显子T等位基因及第4内含子a等位基因与DN^ 的发生密切相关,两种等位基因同时存在者,DN^ 发病风险更高。     

老年人载脂蛋白E基因多态性的分布状态研究

目的：研究载脂蛋白（E（ApoE)基因多态性在老年人群的分布状态,方法：应用聚合酶链－限制性片段长度多态性（PCR－RFLP）方法先扩增出ApoE基因第4外显子内的227bp片段,继以限制性内切酶Cfo I酶解消化,8％聚丙烯酰胺凝胶电泳,最后银染显带判定基因型,并计算等位基因频率,结果：本;实验共检测了正常汉族老年人72例并与88例对照组比较,对照组ε2等位基因频率为5．7％,而71－78岁的老年组中ε2为10．0％,结论：ε2等位基因频率随增龄而增高。     

陕西省老年人群Rb基础的多态性研究

目的 探讨老年人群Ｒｂ基因内含子１７、２０的多态性分布及该位点与衰老的相关性。方法 应用聚合酶链反应（ＰＣＲ）技术先后对老年人（１００例）和青年人（５２例）的Ｒｂ基因１７内含子位点及对老年人（６８例）和青年人（５６例）的Ｒｂ基因２０内含子位点进行检测。结果 在老年组中,Ｒｂ基因１７内含子位点共检测出２个等位基因片段：９４５ｂｐ（Ａ）及６３０＋３１５ｂｐ（Ｂ）,基因型频率：Ａ／Ａ０．２０,Ａ／Ｂ０．     

2型糖尿病并大血管病变患者载脂蛋白B基因多态性研究

目的 研究载脂蛋白B（ApoB）基因变异与2型糖尿病大血管病变的关系。方法 对65例2型糖尿病合并大血管病变患者和60名对照组的 ApoB基因EcoRⅠ和XbaⅠ酶切位点限制性片段长度多态性（PCR－RFLP）进行研究。结果 2型糖尿病大血管病变组载脂蛋白B少见等位基因频率（X^ ,E^-）显著升高，与对照组比较，E^-等位基因频率改变与2型糖尿病患者血脂异常有相关性，X^ 等位基因频率升高与2型糖尿病并大血管病变明显相关。结论 遗传因素在2型糖尿病大血管病变中起重要作用。     

内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点多态性

探讨中国人内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点变异频率及其对血脂、载脂蛋白水平的影响。应用多聚酶链反应对成都地区汉族 2 5 5例正常人和 134例内源性高甘油三酯血症患者apoAⅠ基因启动子 (- 78bp)及内含子I(+83bp)两个MspI限制性片段多态性进行分析。内源性高甘油三酯血症组及对照组载脂蛋白AⅠ基因MspI的多态性以G/G基因型占优势。载脂蛋白AⅠ基因启动子区MspI酶切位点A等位基因频率内源性高甘油三酯血症组显著高于对照组 (0 .35 0比 0 .2 73,P <0 .0 5 ) ,并显著高于欧美的白种人 (0 .30 0vs 0 .12 0～ 0 .191,P <0 .0 1) ,而 +83bpT等位基因则未见差异。在所研究对象中具有A/A基因型者血清甘油三酯水平、甘油三酯 /高密度脂蛋白胆固醇比值及载脂蛋白CⅢ水平较具有G/G及G/A基因型者显著升高 (P <0 .0 5 ) ,血清载脂蛋白CⅡ水平有增加趋势 (P >0 .0 5 )。载脂蛋白AⅠ基因启动子 (- 78bp)MspI酶切位点的突变与中国人内源性高甘油三酯血症有一定关联 ,载脂蛋白AⅠ基因A/A基因型对血清甘油三酯、载脂蛋白CⅡ水平及甘油三酯 /高密度脂蛋白胆固醇比值的升高有一定影响。     

载脂蛋白B、E基因多态性与高血压病、冠心病的相关性研究

目的　探讨载脂蛋白 B、 E基因多态性与高血压、冠心病的相关性。方法　采用聚合酶链反应一限制性片段长度多态性分析 60例正常人、 60例高血压和 2 6例冠心病的载脂蛋白 B、E基因型。结果　高血压组和冠心病组的 Apo B的 Xba I位点等位基因频率高于正常组 ,其中冠心病组与正常组差异明显 ( P<0 .0 5 ) ,Apo E的等位基因 E4高于正常对照组 ( P<0 .0 5和 0 .0 0 5 )。结论　 Apo B的 Xba I位点和 Apo E的等位基因 E4是高血压和冠心病的重要遗传标记 ,推测该两种疾病的发生可能有共同的遗传基础     

载脂蛋白AⅠ-CⅢ基因簇多态性与冠心病的关系

目的 探讨载脂蛋白（apo）AⅠ-CⅢ基因簇多态性与冠心病的关系.方法 应用聚合酶链反应（PCR）技术检测104例汉族健康人和47例冠心病患者的apoAⅠ-CⅢ基因区域PstⅠ、SacⅠ酶切位点上限制性片段长度多态性（RFLPs）及血脂、脂蛋白含量.结果 冠心病组P-等位基因频率（0.117）显著高于对照组（0.067,P＜0.05）,P-等位基因与冠心病患者血清LDL-C升高及HDL-C降底有相关趋势.冠心病组S＋等位基因频率（0.309）稍高于对照组的（0.274）.结论 apoAⅠ基因PstⅠ位点的P-等位基因可能是冠心病的遗传易患因子.     

Gastric cancer in a Caucasian population： Role of pepsinogen C genetic variants

AIM: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS: The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp). RESULTS: Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P < 0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P < 0.001) or invasive GC (OR = 0.39; P = 0.004). CONCLUSION: Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.     

Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in ankylosing spondylitis

OBJECTIVE: Since ulcerative colitis and Crohn's disease, which are associated with ankylosing spondylitis (AS), have been found to be variably associated with the IL-1B and the IL-1RN genes encoding interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra), we have investigated whether these polymorphisms in IL-1B and IL-1RN are also involved in AS. METHODS: DNA was isolated from peripheral blood of 106 patients with AS and 104 healthy controls. All patients and controls were Dutch Caucasians. Bi-allelic polymorphisms at positions +3,953 and -511 in the IL-1B gene, and a penta-allelic polymorphism in intron 2 of the IL-1RN gene were studied by polymerase chain reaction-based methods. RESULTS: Allele IL-1RN*2 was significantly increased in AS (odds ratio=1.60; 95% confidence interval=1.20-2.80; P=0.031) compared with healthy controls, and independent from the polymorphism in loci IL-1B-511 and IL-1B+3,953. No significant associations were found between AS and the IL-1B-511 or IL-1B+3,953 polymorphisms. CONCLUSION: Similar to other chronic inflammatory diseases, AS is associated with the IL-1RN*2 allele. Further studies are necessary to determine the biological significance of these findings in relation to susceptibility or severity of the disease.     

Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India

The objective of this study was to assess the frequency of factor VIII (FVIII) gene intron 1 and intron 22 inversions and the informativeness of polymorphic markers for the genetic diagnosis of patients with haemophilia A (HA). Fifty unrelated patients with HA were first assessed for the intron 1 and intron 22 inversion mutations. Inversion-negative families were then screened for the bi-allelic intragenic markers--intron 7 G-->A polymorphism, HindIII site in intron 19 and XbaI site in intron 22 and the multiallelic dinucleotide CA repeat alleles in introns 13 and 22. The extragenic, multiallelic VNTR DXS52 (st14) was also analysed. Intron 22 inversion mutation was found in 38% (n = 19) of all patients and 46% of those with severe HA. Intron 1 inversion was found in one (2%) patient. Of the 30 inversion-negative families, XbaI site polymorphism was the single most informative marker (70%, n = 21/30) followed by HindIII (60%, n = 18/30), intron 13 CA repeats (56.66%, n = 17/30), intron 22 CA repeats (50%, n = 15/30), DXS52 VNTR (23.33%, n = 7/30) and intron 7 G-->A polymorphism (6.66%, n = 2/30). The combined use of these markers was informative in 92% (n = 46/50) of HA families. Based on the informativeness of these markers a comprehensive algorithm has been proposed for genetic diagnosis of HA in India.     

PAI-1基因启动子区4G/5G基因多态和Enos第4内含子a/b基因多态与糖尿病肾病的相关性研究

为探讨 PAI- 1基因启动子区 4 G/ 5 G基因多态性、一氧化氮合酶 (e NOS)第 4内含子 2 7bp插入 /缺失 (a/b)多态性与糖尿病肾病 (DN)的相关性 ,采用发色底物法测定 PAI- 1活性 ;等位基因特异性引物 PCR扩增技术测定 PAI- 1基因 4 G/ 5 G多态性 ;聚合酶链反应测定 e NOS基因第 4内含子 2 7bp的 a/ b多态性。结果显示 ,Hb A1c、SBP、TC、e NOS基因第 4内含子 a/ b多态均属 DN的独立危险因素。早期糖尿病肾病组 (DN+组 ) a等位基因及 ab基因型频率显著高于糖尿病非肾病组 (DN-组 ) (P<0 .0 5 )。DN+组血浆 PAI- 1活性明显高于 DN-组 (P<0 .0 5 ) ;4 G纯合子组 PAI- 1活性明显高于 4 G/ 5 G杂合子及 5 G纯合子组 (P<0 .0 0 5 )。2型糖尿病患者中 ,4 G纯合子和a/ b杂合子携带者 DN的相对风险明显增加 (P<0 .0 5 ) ,4 G杂合子携带者 DN的相对风险增加不明显 (P>0 .0 5 )。当 a/ b杂合子和 4 G纯合子基因多态并存时 DN的发病风险明显增加。认为 PAI- 1基因启动子区 4 G/ 5 G基因多态、e NOS基因第 4内含子 a/ b多态与 DN的发生、发展有关。两种基因多态同时存在时 ,DN的发病风险明显增加     

Identification and characterization of a novel large insertion/deletion polymorphism of 1464 base pair in the human thyroglobulin gene.

We identified a novel large insertion/deletion (Indel) polymorphism of 1464 bp localized in intron 18 of the human thyroglobulin gene. Data from sequence showed a high A+T content (62%), two 17-bp long motif repeats, and three different types of 10-bp long palindromic sequences. The comparison between these 1464 bp and sequences deposited in National Center for Biotechnology Information (NCBI)/GenBank database exhibit a nonsignificant degree of homology with any previously described sequences. The long polymerase chain reaction (PCR) method was used to amplify the genomic DNA region containing intron 17/exon 18/intron 18/exon 19/intron 19 by primers situated in the introns 17 and 19. The amplification generates two fragments of 3.5 and 5.0 kb that correspond to the exclusion or inclusion of a 1464-bp segment, respectively. Both variants are thus widely represented in the human population; giving allele frequencies of 0.56 (insertion) and 0.44 (deletion). Finally, the polymorphism was confirmed by sequence analysis of the 5.0- and 3.5-kb amplified fragments.     

雌激素受体基因多态性与冠心病关系的研究

目的　观察雌激素受体 (ER)基因多态性在中国汉族人群中的分布及其与冠心病 (CHD)的关系。方法　应用聚合酶链反应 (PCR)和限制性片段长度多态性 (RFLP)方法检测 1 35例CHD患者和 1 1 8例正常对照者ER基因型 ,结合血脂水平、选择性冠状动脉造影 (SCA)结果探讨两者间的关系。结果　ER等位基因X、x和P、p频率在冠心病组和对照组分别为 0 1 70、0 830 ,0 1 69、0 831 ;0 2 56、0 744,0 339、0 661。基因型频率分布符合Hardy Weinberg平衡定律。XbaⅠ酶切多态性基因型频率、等位基因频率及结合XbaⅠ和PvuⅡ两个酶切多态性分析在组内、组间比较差异均无显著性 (P >0 0 5) ,且ER基因型间血脂水平、SCA结果在组内比较均无统计学意义 (P >0 0 5)。但是 ,PvuⅡ酶切多态性在正常对照组与CHD组以及心肌梗死组与心绞痛组比较有明显差异 (P <0 0 5)。结论　在CHD人群中存在着ERXbaⅠ和PvuⅡ基因多态性 ,其中XbaⅠ酶切多态性与CHD无相关性 (P >0 0 5) ,而ERPvuⅡ酶切多态性与冠心病有相关性 (P <0 0 5) ,PvuⅡ基因多态性可能是CHD发病的危险因素之一。     

Oestrogen receptor alpha gene polymorphism is related to aortic valve sclerosis in postmenopausal women

OBJECTIVES: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women. DESIGN: Case-control study. SUBJECTS AND METHODS: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years. RESULTS: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04). CONCLUSIONS: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.     

Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe preeclampsia.

Associations have been reported between estrogen receptor alpha (ESR1) gene polymorphisms and various pathological conditions, including cardiovascular diseases. Our aim was to investigate whether two polymorphisms of the ESR1 gene (ESR1 c.454 -397T>C: PvuII restriction site and c.454 -351A>G: XbaI restriction site) are associated with preeclampsia. In a case-control study, we analyzed blood samples from 119 severely preeclamptic patients and 103 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. All of the women were Caucasian. There was no association between severe preeclampsia and the PvuII and XbaI ESR1 gene polymorphisms separately. However, with the simultaneous carriage of both polymorphisms, the TT/AA genotype combination was significantly more frequent in severely preeclamptic patients than in healthy control subjects (24.4% vs. 9.7%, p=0.003), whereas the TT/AG combination was significantly less frequent in the severely preeclamptic group than in the control group (5.0% vs. 18.4%, p=0.002). According to the haplotype estimation, the homozygous T-A haplotype carriers had an increased risk of severe preeclampsia independent of maternal age, prepregnancy BMI, primiparity and smoking status (adjusted odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.65-11.53). The GG genotype of the XbaI polymorphism was associated with a lower risk of fetal growth restriction in patients with severe preeclampsia (OR: 0.23, 95% CI: 0.07-0.73). In conclusion, the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed an increased risk of severe preeclampsia. In addition, the GG genotype of the XbaI polymorphism decreased the risk of fetal growth restriction in severely preeclamptic patients.