Estrogen receptor alpha gene polymorphism associated with type 2 diabetes mellitus and the serum lipid concentration in Chinese women in Guangzhou

Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the XbaⅠ and PvuⅡ restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ER0t gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51--70 years. ESR1 genotyping was performed using polymerase chain reaction （PCR） and PvulI and XbaI restriction fragment length polymorphism （PCR-RFLP） analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuⅡ, but not XbaⅠ, allele frequency between the type 2 diabetes mellitus and control groups （P=0.001 and P=0.122）. When the group was separated into men and women, the difference was significant in women （P〈0.001） but not in men （P=0.854） with the PvulI genotype, and the effect of PvulI variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvulI genotype was associated with blood glucose [fasting blood glucose （FBG）, postprandial blood glucose （PBG）] and serum lipid [total cholesterol （TC） and low density lipoprotein （LDL）-c] concentration in healthy women. Conclusions PvuII polymorphism of ESRI increases susceptibifity to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.     

Relationship between matrix metalloproteinase-9 polymorphism and acute coronary syndrome

Objective： To investigate the relationship of matrix metalloproteinase-9 polymorphism to acute coronary syndrome and its affect on the severity of coronary artery disease. Methods： By means of polymerase chain reaction （PCR） and restriction fragment length polymorphism, genotypes of 245 patients with acute coronary syndrome（ACS） and 205 healthy subjects were tested. Genotypes displaying C-1562T functional promoter polymorphism （of the MMP-9 gene） were determined. The relationship between the polymorphism of the MMP-9 gene and ACS and the severity of coronary vessels diseased was analyzed. Results： The frequency of C/T plus T/T genotypes and T allele in patients with ACS was significantly higher than that in healthy subjects （22.1% vs 12.7% and 11.4% vs 6.6% respectively）. But they were not associated with the number of coronary arteries diseased. Conclusion： The MMP-9 polymorphism may be susceptible to ACS. But there was not significant difference between the AMI and UAP subgroups.     

Association between C-reactive protein gene ＋1059 G/C polymorphism and the risk of coronary heart disease： a meta-analysis

Background C-reactive protein （CRP） gene ＋1059 G/C polymorphism has been reported to be associated with coronary heart disease （CHD） risk, but the results remain inconclusive. This meta-analysis was therefore conducted to clarify these controversies. Methods A comprehensive search was conducted to identify all case control studies on the association between CRP gene ＋1059 G/C polymorphism and CHD risk. All the related studies were further strictly selected according to the inclusion criteria. Meta-analysis was performed with STATA 10.1 （StataCorp, USA）. The association was assessed by odds ratio （OR） and 95% confidence interval （C/）; both Begg＇s funnel plot and Egger＇s regression test were used to assess the publication bias. Results This meta-analysis on a total of 13 studies comprising 6316 CHD cases and 4467 controls showed no significant association between CRP gene ＋1059 G/C polymorphism and CHD risk in the overall study （for C/C＋C/G vs. G/G： OR=1.01, 95% C/=0.81-1.25, P=0.96; for C/C vs. C/G＋G/G： OR=1.17, 95% C/=0.77-1.77, P=0.47; for C/C vs. G/G： 0R=1.17, 95% C/=0.77-1.77, P=0.47; for C allele vs. G allele： 0R=1.01, 95% C/=0.81-1.24, P=-0.96）. However, in the subgroup analysis by ethnicity, the results showed significant association between CRP gene ＋1059 G/C polymorphism and CHD risk among Caucasians （for C/C vs. G/G： OR=2.54, 95% C1=1.13-5.72, P=0.02; C/C vs. C/G＋G/G： OR=2.45, 95% C1=1.09-5.51, P=-0.03）, but not among Asians and Africans （P 〉0.05）. Conclusion CRP gene ＋1059 G/C polymorphism may be associated with increased CHD risk among Caucasians and more evidences need to validate the conclusion.     

Study on relationship between polymorphism of hAR gene（CAG）n micro—satellite and prostate cancer

Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of PCa were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 PCa, and the (CAG)n repeats in 36 PCa which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among variou     

Relationship between cystathionine γ-lyase gene polymorphism and essential hypertension in Northern Chinese Han population

Background Hydrogen sulfide （H2S） plays an important role in the smooth muscle cell relaxation and thereby participates in the development of hypertension. Cystathionine γ-lyase is the key enzyme in the endogenous production of H2S. Up to now, the reports on the relationship between the polymorphisms of cystathionine γ-lyase gene （CTH） and essential hypertension （EH） are limited. This study was designed to assess their underlying relationship.
Methods A total of 503 hypertensive patients and 490 age-, gender- and area-matched normotensive controls were enrolled in this study. Based on the FASTSNP, a web server to identify putative functional single nucleotide polymorphisms （SNPs） of genes, we selected two SNPs, rs482843 and rs1021737, in the CTH gene for genotyping. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method （PCR-RFLP）. The frequencies of the alleles and genotypes between cases and controls were compared by the chi-square test. The program Haplo.stats was used to investigate the relationship between the haplotypes and EH.
Results These two SNPs were in Hardy-Weinberg Equilibrium in both cases and controls. The genotype distribution and allele frequencies of them did not significantly differ between cases and controls （all P〉0.05）. In the stepwise logistic regression analysis we failed to observe their association with hypertension. In addition, none of the four estimated haplotypes or diplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors.
Conclusions The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. However, replications in other populations and further functional studies are still necessary to clarify the role of the CTH gene in the pathogenesis of EH.     

Relationship between MDR1 polymorphism and blood concentration of cyclosporine A

Ithough renal grafts＇ survival and functioning have been improved with the introduction of cyclosporine A （CsA） into the immunosuppression treatment, its long-term results are still failing to meet treatment expectations. One of the important reasons is that the bioavailability of CsA varies largely among different patients but the use of CsA is not individualized. The human multidrug resistance gene-1 （MDR1） encodes P-glycoprotein （P-gp） that is responsible for resistance to foreign body and plays important roles in the absorption,     

Others——Single nudeotide polymorphism of calcitonin receptor gene and idiopathic hypercalciuria

Objective To explore the association of the calcitonin receptor （CTR） allelic polymorphism in the 1 377 bp region with the risk of idiopathic hypercalciuria （IH） in the Han nationality in Hubei area, and to study the pathogenesis of IH. Methods The CTR genotypes were determined by polymerase chain reaction-restriction flagment length polymorphism in 76 patients with IH and 126 healthy controls from the Han nationality in Hubei area, using restriction endonuclease AluI. Results The distri bution frequencies of AluI alleles in the 2 groups followed the Hardy-Weinberg equilibrium. The distribution frequencies of the CC, TC and TT genotypes were 73.7%, 17.1% and 9.2% in IH patient group, and 89.7%, 9.5 % and 0.8 % in control group; the distribution frequencies of C and T alleles in the 2 groups were 84.2 %, 15.8 % and 94.4 %, 5.6 %, respectively. The distribution frequencies of T and TT alleles were higher, while those of C and CC alleles were lower, compared with control group;the differences between the 2 groups were significant （P 〈 0.05）. Conclusion The results indicate that the C/T single nucleotide polymorphism in the CTR gene play a significant role in the mechanism of IH in the Han nationality in Hubei area in China. 7 refs,2 figs,2 tabs.     

Relationship between gene polymorphisms of IL-1β or IL-1RN and gastroesophageal reflux disease

目的 研究胃食管反流病(GERD)患者白细胞介素1B(IL-1β)基因和白细胞介素1受体拮抗剂(IL-1RN)基因的基因多态性情况,并分析各种基因型与GERD的发病风险、内镜下表现的相关性.方法 采用病例对照研究方法,收集154例GERD患者和160例健康人外周静脉血,提取DNA,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法 检测IL-1β-511基因型,采用聚合酶链式反应 (PCR)方法 测定IL-1RN基因型,比较各种基因型及各等位基因的分布情况.结果 IL-1β-511基因多态性及各等位基因与GERD患病风险均无相关性; IL-1RN*1,2基因型及2等位基因可能增加GERD患病风险(P<0.05);IL-1β-511*T/IL-1RN*1(T1) 可能降低GERD患病风险(P<0.05),其他各组基因型差异均无显著性;IL-1β-511-CC基因型及C等位基因频率在NERD组明显高于反流性食管炎组,差异有显著性(P<0.05),在没有Hp感染时,这种差异更明显.结论 IL-1β和IL-1RN基因多态性与GERD的患病风险、内镜下表现之间具有相关性.     

血管紧张素原基因M235T多态性与冠心病的相关性研究

目的研究血管紧张素原基因M235T多态性与冠心病的关系。方法应用多聚酶链反应结合限制性内切酶法(PCRRFLP)对100名经冠脉造影确诊为冠心病(CHD)的患者(其中47名有心肌梗死病史)和52名冠造结果正常及18名门诊常规体检且无冠心病史者进行病例-对照研究,并进行多因素分析。结果病例组与对照组基因型分布及等位基因频率均有显著差异(P<0.01),CHD组TT基因型和T等位基因频率显著高于对照组(分别为0.67,0.79vs0.44,0.63),在心肌梗死患者中更明显(分别为0.74,0.85vs0.44,0.63)。性别对冠心病的发病也有影响,男性患冠心病发病的危险性是女性的1.899倍。结论AGT基因变异与CHD发病具有相关性。T等位基因是CHD的危险因素,可增加冠心病发病的2.059倍。性别也可作为冠心病的危险因素。     

雌激素受体α基因多态性与原因不明月经过少的相关性研究

目的:探讨西南地区雌激素受体α(estrogen receptor α,ERα)基因多态性与原因不明月经过少的关系。方法:选择西南地区100名原因不明月经过少患者为实验组,100名月经正常者作为正常对照组。应用分子生物学的方法分析ERα基因1号内含子内切酶PvuⅡ,XbaⅠ限制性片段长度多态性(restriction fragment length polymorphism,RFLP),观察ERα基因多态性基因型在实验组与对照组中的基因型分布。结果:P基因型频率实验组为47.5%,对照组为30.5%(OR=1.810,P=O.012)。X基因型频率实验组为20.5%,对照组为32.0%(OR=0.641,P=0.036);PvuII和XbaI限制性片段长度多态性在两组中均呈多态性分布。结论:ERα基因多态性与原因不明月经过少有关,P等位基因可能是其危险因素;X等位基因可能是其保护因素。     

PA PP-A 的表达及基因多态性与冠心病患者冠状动脉病变程度的关系

目的：探讨妊娠相关血浆蛋白A（PAPP‐A）的表达及基因多态性与冠心病患者冠状动脉（以下简称冠脉）病变程度的关系。方法选取来河南省南阳市中心医院就诊的冠心病患者98例（观察组）,根据冠脉造影检查结果将患者分为单支病变组和多支病变组。选取同期来该院健康体检者98例（对照组）,分别于患者就诊时和对照组体检时抽取静脉血,采用ELISA法检测血清PAPP‐A的蛋白水平,聚合酶链式反应‐限制性片段长度多态性（PCR‐RFLP）检测PAPP‐A基因的IVS6＋95多态性。结果与对照组比较,观察组患者外周血PA PP‐A蛋白水平明显升高（ P＜0．05）,而多支病变组患者外周血PA PP‐A蛋白水平明显高于单支病变组患者（P＜0．05）。外周血PAPP‐A水平与冠脉病变程度呈正相关。PAPP‐A基因IVS6＋95位点存在3种基因型,包括CG杂合型、CC纯合型和GG纯合型。其中多支病变患者CC纯合型位点基因频率明显高于单支病变组患者（ P＜0．05）。结论 PAPP‐A蛋白水平及IVS6＋95多态性与冠心病患者冠脉病变程度存在密切关系,CC基因型患者可能是冠心病患者遗传易感性基因标志之一。     

E-选择素Leu554Phe基因多态性与冠心病发病的相关性研究

目的 研究辽宁西部地区汉族人群E-选择素基因Leu554Phe多态性,探讨该多态性与冠心病(CHD)发病的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测118例冠心病患者和125例正常对照者E-选择素基因型,生化技术测定血脂水平.结果 E-选择素基因型LL、LF、FF频率在病例组和对照组分别为84.75％,12.71％,2.54％和93.60％,6.40％,等位基因L、F频率在病例组和对照组分别为91.10％,8.90％ and 96.80％,3.20％.其基因型频率和等位基因频率在冠心病组和对照组比较均有显著性差异(P＜0.05).基因型频率的相对风险分析,LL+LF基因型患冠心病的风险是LL基因型的4.980倍(OR=2.633,95％CI:(1.098～6.312).结论 辽宁西部地区汉族人群E-选择素存在基因Leu554Phe多态性;E-选择素Leu554Phe基因多态性与冠心病的发病有相关性,F等位基因可能是冠心病发病的危险因素之一.     

新疆维吾尔族妇女子宫内膜异位症和雌激素受体基因多态性的关系

目的:探讨雌激素受体(ER)基因多态性在新疆维吾尔族(维族)妇女中的分布及其与子宫内膜异位症(内异症)的遗传易感性的关系。方法:应用PCRRFLP技术,检测107例维吾尔族健康妇女(对照组)及65例经腹腔镜或手术证实为内异症患者(内异症组)的ER基因XbaⅠ和PvuⅡ酶切多态性。两组检测对象均为世居新疆的维吾尔族妇女。结果:ER基因型频率分布符合Hareyweinberg平衡定律。ER等位基因X、x和P、p在内异症组与对照组频率分别为0.223、0.777、0.231、0.769和0.168、0.832、0.341、0.659。ER基因PvuⅡ酶切多态性基因型频率、等位基因频率在内异症组与对照组间的差异有统计学意义(P<0.05);两组XbaI酶切多态性基因型频率、等位基因频率的差异无统计学意义(P>0.05);ER基因XbaⅠ和PvuⅡ组合基因型分布在组间、组内分布的差异无统计学意义(P>0.05)。结论:ER基因XbaⅠ酶切多态性与维族妇女内异症发病无关,而PvuⅡ酶切多态性与内异症发病有关。PvuⅡ基因多态性可能是维族妇女子宫内膜异位症发病的危险因素之一。     

基质金属蛋白酶9基因多态性与冠心病的关联性

目的：探讨基质金属蛋白酶9（MMP-9）基因C1562T、R279Q单核苷酸多态性(SNPs)与冠状动脉粥样硬化性心脏
病(CHD)的相关性。方法：258例CHD患者和183例健康体检者作为研究对象,采用酶联免疫吸附试验（ELISA）测定血清MMP-9水平,应用聚合酶链式反应-限制性片段长度多态（PCR-RFLP）方法对MMP-9基因C1562T和R279Q多态位点进行SNPs基因型检测,运用统计学软件SPSS 17.0分析等位基因和基因型频数分布。结果：CHD组患者血清MMP-9水平明显高于健康对照组（P<0.05）。CHD 组MMP-9基因C1562T多态位点CT+TT基因型和T等位基因频数（24.4%和11.8%）明显高于健康对照组（13.8%和7.3%）（P<0.05）。CHD组MMP-9基因R279Q多态位点G+GG基因型和G等位基因频数（60.2%和41.7%）与健康对照组（68.0%和41.5%）比较差异无统计学意义（P>0.05）。结论：CHD患者伴有MMP-9　的过度释放,MMP-9基因C1562T多态位点与CHD发病有关联,R279Q多态位点与
CHD发病无关联。     

P-选择素基因多态性与冠心病的相关性

目的研究P-选择素基因多态性与冠心病（coronaryheartdisease,CHD）易感性之间的相关性。方法以2012年6月-2013年4月辽宁医学院附属第-医院心内科病房的200例冠心病患者为病例组,210例健康体检者为对照组,应用聚合酶链反应-限制性片段长度多态性（polymerasechainreaction—restrictionfragmentlengthpolymorphism,PCR—RFLP）方法和DNA测序法,检测两组人群P-选择素基因启动子区-2123C／G、-1969G／A和-1817T／C的基因多态性,并将冠心病组分为心绞痛、心肌梗死和缺血性心力衰竭组,研究不同类型冠心病组与对照组之间P-选择素基因启动子区-2123C／G、-1969G／A和-1817T／C位点基因多态性分布的差异。结果P-选择素基因-2123C／G位点基因型和等位基因频率在冠心病组和对照组间的分布差异有统计学意义（x2=6．124,P=0．047;x2=7．355,P=0．008）,并且在心肌梗死组与对照组、缺血性心力衰竭组与对照组的分布差异也具有统计学意义（x2=6．473,P=0．039;x2=13．944,P=0．001）。-1817T／C和-1969G／A位点基因型和等位基因频率在冠心病组和对照组间以及不同类型冠心病组和对照组间的分布差异均无统计学意义俨〉0．051。结论P-选择素基因-2123C／G位点多态性与冠心病易感性之间具有相关性。     

ApoE基因多态性与冠心病的相关性研究

目的 研究ApoE基因多态性与冠心病(CHD)的相关性.方法 随机选择潍坊地区汉族人88例CHD患者与75例健康对照者,抽取空腹静脉血测定CHD患者及健康对照者的TC、TG、HDL-C、LDL-C、ApoA1、ApoB-100等6项血脂代谢指标,应用改良的聚合酶链反应-限制性片段长度多态性分析及聚丙烯酰胺凝胶电泳法检测ApoE基因型.结果 ①共发现5种ApoE基因型,分别为E2/3,E3/3,E3/4,E2/4,E4/4,未发现E2/2,两组中均以E3/3分布最高.②CHD组ApoE2/4,E4/4基因型频率明显高于对照组,而ApoE3/3基因型频率低于对照组,而ε2,ε4等位基因频率CHD组高于对照组,ε3等位基因频率低于对照组.结论 ApoE基因多态性与血脂代谢及与CHD的发生密切相关.ε4等位基因是CHD发病的遗传易感因子,ε2等位基因是预防CHD发生的保护因子.ApoE基因多态性可能通过影响ApoE水平而实现CHD致病作用.     

ABCA1基因C69T多态与冠心病关联研究

目的　探讨ATP BindingCassetteTransporter 1(ABCA1)基因C69T多态与汉族冠心病(CHD)的关系。方法　以2 64例CHD患者和2 78例性别、年龄匹配的正常人为对象进行病例 对照研究;采用PCR RFLP技术对ABCA1基因C69T多态位点进行分析。结果　ABCA1基因C69T多态在CHD组与对照组分布无显著性差异(P >0 .0 5 ) ;CC基因型和T等位基因携带者间各项血脂水平及心血管事件发生率比较均无差异显著性。结论　ABCA1基因C69T多态性与汉族人群CHD不存在关联。     

高血压合并冠心病与AT1R基因多态性的关系

目的探讨血管紧张素Ⅱ的1型受体(AT1R)基因多态性与高血压患者合并冠心病(CAD)的关系.方法采用PCR-RDLP法,检测123例高血压患者(其中48例合并冠心病)和148例健康对照的AT1R基因型.结果高血压患者中无论是否合并冠心病,其AT1RA1166C基因型分布均与对照组无显著性差异(均为P＞0.05).高血压合并冠心病组与无冠心病组之间的AT1R基因型分布亦无显著差异(P＞0.05).结论AT1R基因A1166C多态性与中国人高血压病发生及高血压患者是否易患冠心病无关.