儿茶酚-O-甲基转移酶基因多态性在新疆伊犁地区人群中的分布及与食管鳞癌的关系

目的 探讨儿茶酚-O-甲基转移酶(COMT)基因Vall58Met多态性在新疆伊犁地区人群中的分布及与食管鳞癌(ESCC)的关系.方法 研究对象共487例,包括169例ESCC,318例正常对照.采用病例-对照研究方法,以聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析COMT基因G/A(Val/Met)多态性.结果 487例新疆伊犁地区受试者COMT基因型频率分布依次为GG型50.7%,GA型41.1%,AA型8.2%;等位基因G为71.3%,A为28.7%;分层分析显示,新疆伊犁地区年龄≤60岁的ESCC组与对照组之间差异有统计学意义(P＜0.05);将年龄及性别校正后,ESCC组与对照组COMT Vall58Met多态性于哈族、汉族差异均无统计学意义(P＞0.05).结论 COMT基因Vall58Met多态性可能不是新疆伊犁地区哈萨克族、汉族ESCC危险性的遗传标志.

Abstract：

Objective To explore the distribution of Vall58Met polymorphism in catechol-O-methyltransferase (COMT) gene and its genetic susceptibility for esophageal squamous cell carcinoma (ESCC) of Yili population. Methods A case-control study was designed with 487 samples from 169 ESCC patients and 318 controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approaches. Results The frequencies of COMT Vall58Met polymorphism GG,GA and AA genotype were 50. 7% , 41. 1% and 8. 2% in all subjects, and the frequencies of allele were 71. 3% (G), 28. 7% (A). Stratified analysis by less than 60 years old showed that there were statistically significant differences in both frequencies of COMT Vall58Met polymorphism and allele between controls and ESCC group in Yili Prefecture, Xinjiang (P＜0. 05). After adjusting age and gender, there was no difference in Vall58Met polymorphism in Kazakh and Han ethnics between ESCC group and control group (P＞0. 05). Conclusion There was no association of genetic polymorphisms in the COMT Vall58Met with risk of ESCC of Kazakh and Han ethnics of Yili Prefecture, Xinjiang.     

胃癌患者髓过氧化物酶基因多态性分析

目的 探讨髓过氧化物酶(MPO)基因多态性与胃癌发病的关系.方法 按照病例对照研究的方法,收集62例胃癌患者和61名健康对照者外周血标本,提取DNA进行MPO-463位点基因多态性检测.结果 MPO-463 GG、GA和AA 3种基因型的频率在胃癌组中分别为87.1%、11.3%和1.6%,在对照组中分别为72.1%、23.0%和4.9%;将携带MPO-463 GA和AA型者合并后与携带MPO-463 GG型相比较,患胃癌的风险显著增高(P=-0.039,DR=0.383,95%CI:0.151-0.972).相对于G等位基因,携带A等位基因的个体患胃癌的风险显著降低(P=0.026,OR:0.399,95%CI:0.174～0.916).结论 MPO-463 G/A多态性与胃癌的发生有关,其中A基因是一个保护基因.

Abstract：

Objective To investigate the association of myeloperoxidase (MPO) genetic polymorphism and gastric cancer. Methods A case-control study was performed including 62 patients with gastric cancer and 61 healthy controls. Peripheral blood was collected for genetic analysis of MPO-463. Results There were no significant differences in gender, age, and smoking between the two groups (P>0.05). However, the two groups differed in drinking, family history of gastric cancer, and Helicobacter pylori(HP) infection(P<0.05). The frequencies of MPO-463GG, GA and AA were 87.1%, 11.3% and 1.6%in the study group, and were 72.1% , 23.0% , and 4.9% in the control group, respectively. Carriers of MPO-463 GA or AA had a significantly higher risk of gastric cancer than those of MPO-463 GG (x2=4.253, P<0.05, OR=0.383, 95% CI:0.151-0.972). Carriers of G allele had a significantly lower risk of gastric cancer compared to carriers of A allele (x2=4.935,P<0.05, OR =0.399,95% CI:0.174-0.916). Conclusion MPO-463 G/A polymorphism is associated with gastric cancer with A being a protective gene.     

食管鳞癌遗传易感性与基质金属蛋白酶-1基因多态性的关系

目的 探讨基质金属蛋白酶-1(MMP-1)基因多态性与食管鳞癌发病风险的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测450对病例与对照中MMP-1的1G/2G基因多态性.结果 与1G等位基因携带者(包括1G/1G及1G/2G基因型)比较,2G/2G基因型携带者与食管鳞癌显著相关[OR=1.39;95%可信区间(CI):1.06～1.81].此外,食管鳞癌的发病风险在吸炳者及女性中更加显著,其OR及95%CI分别为1.59(1.09～2.31)及1.76(1.05～2.97).结论 MMP-1基因多态性可能在食管鳞癌的发生过程中起到一定作用.

Abstract：

Objective Our study aimed to test the association between the matrix metalloproteinase-1 ( MMP-1) polymorphism and risk of esophageal squamous cell carcinoma ( ESCC ) . Methods We determined the MMP-1 polymorphism in 450 ESCC cases and 450 frequency-matched controls by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results We found evidence for a significant association between the 2G/2G genotype and ESCC risk compared with 1G allele,including 1G/1G genotype and 1G/2G genotype [OR = 1. 39;95% confidence interval (CI), 1. 06-1. 81].Furthermore,the increased risk was found to be in smokers (OR,1. 59;95% CI, 1. 09-2. 31) and in female (OR, 1.76;95% CI, 1.05-2. 97). Conclusion Our study suggests that the MMP-1 promoter polymorphism may play a role in the etiology of ESCC.     

膀胱癌易感性与髓过氧化物酶基因-463G>A 多态性的关系

目的 探讨髓过氧化物酶(MPO)基因-463G＞A多态性与中国苏皖地区汉族人群膀胱癌易感性的关系.方法 采用面访填写调查表及采用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)方法 检测年龄和性别匹配的中国苏皖地区汉族354例膀胱癌患者和360例正常人群的MPO一463G＞A基因型.通过分层分析探讨年龄、性别和吸烟对罹患膀胱癌的影响.结果 与-463GG比较,携带MPO-463GA/AA基因型者可降低罹患膀胱癌的危险性(OR=0.72,95%CI=0.54-0.99).分层分析结果显示,年龄60岁的男性在吸烟下携带-463GA/AA基因型具有保护作用(年龄60岁:OR=0.37,95%CI=0.22-0.61;男性:0.66,95%CI=0.47-0.97;吸烟:0.64,95%CI:0.41-0.99).结论 MPO-463G＞A多态性可能与我国苏皖地区汉族人群膀胱癌发生有关.     

脓毒症易感性与IRAK-M基因多态性的相关性

目的 探讨脓毒症易感性与IRAK-M基因多态性的关系.方法 选择脓毒症患者82例为实验组,118例健康人群为对照组.应用聚合酶链反应(PCR)-限制性片段长度多态性分析法(RFLP)分析IRAK-M+22148G＞A基因多态性.结果 脓毒症组IRAK-M+22148G＞A位点G/G基因型频率高于对照组(81.7%比28.8%),差异有统计学意义(P＜0.01),G等位基因频率高于对照组(84.1%比33.9%,P＜0.01),差异有统计学意义,脓毒症组肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平高于对照组[(843.00±97.34)ng/L比(287.00±79.12)ng/L;(741.00±65.61)ng/L比(194.00±58.47)ng/L],差异有统计学意义(P＜0.05);G/G基因型与脓毒症之间有明显相关(OR=11.03,95%CI:5.55～21.94).结论 IRAK-M+22148G/A基因多态性与脓毒症的易感性相关,G/G基因型者易患脓毒症.

Abstract：

Objective To determine the association between the genetic polymorphisms of IRAK-M and the susceptivity of sepsis. Methods Two candidate gene loci in + 22148G ＞ A patients with 82 sepsis infection and 118 heahhy controls were investigated. The polymorphisms were assessed by the polymerase chain reaction (PCR) and the restrict fragment length polymorphisms (RFLP). Results In sepsis group and control group, the frequency of G/G gene was 81.7% and 8. 8% ( P ＜0. 01 ) and that of G allele was 84.1% and 33.9% ( P ＜0. 01 ), respectively. The levels of tumor necrosis factor (TNF) -α and interleukin (IL) -6 in sepsis group were higher than in control group [ ( 843.00±97.34) vs (287.00±79.12) ng/L;(741.00±65.61) vs (194.00±58.47)ng/L,P＜0.05].The G/G genotype was associated with sepsis (OR=11.03,95% CI=5.55-21.94).Conclusion The genetic polymorphism of +22148 site of IRAK-M gene is associated with the susceptivity of sepsis.The G/G genotype is susceptive to sepsis.     

食管癌易感性与白细胞介素-8基因多态性的关系

目的 探讨白细胞介素(IL)-8多态性与食管癌发生危险因素的关系.方法 采用以医院为基础的病例对照研究方法,以高分辨率熔解曲线(HRM)小片段扩增子法分析351例食管癌和384例非肿瘤对照IL-8基因多态性,计算各种基因型的食管癌发生风险及其95%可信区间.结果 IL-8-251(A/T)多态3种基因型TT、AT、AA在食管癌组和非肿瘤对照组的频率分别为39.9%(IT)、54.7%(AT)、5.4%(AA)和43.8%(TT)、45.3%(AT)、10.9%(AA),与携带IL-8-251TT基因型的个体比较,IL-8-251 AA等位基因型可以减少46%食管癌的发病风险.结论 IL-8-25l(A/T)基因多态性AA基因型可能是食管癌发生的保护性因素.

Abstract：

Objective To investigate the relationship between interleukin-8 (IL-8) polymorphism and the susceptibility to esophageal cancer in a Chinese Han population. Methods Genotypes were determined by the high resolution melting (HRM) method in 351 esophageal cancer cases and 384 controls without cancers. Results The IL-8 genotype frequency was 39. 9% ( TF), 54. 7% (AT), 5.4% (AA)in the esophageal cancer group, and 43.8% (TT), 45. 3% (AT), 10. 9% (AA) in the control group respectively. Logistic regression analyses revealed that the risk associated with IL-8 variant genotype was 0. 54 (95% CI =0. 30-0. 98) for IL-8 AA compared with its wild-type homozygote. Conclusion IL-8 AA polymorphism may serve as a protective biomarker of esophageal cancer susceptibility.     

冠心病与内皮型一氧化氮合酶基因多态性的关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因-786T/C,4a4b,894G/T等3个多态性位点与冠心病(CAD)发病相关.方法 对146例中国汉族人群CAD患者和113例正常对照进行遗传学分析,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR技术分析2个SNP位点即-786T/C和894G/T,以及1个VNTR位点4a4b,检测各位点基因型和等位基因频率,采用HaploView 4.0及SPSS 13.0软件经x2检验比较两组间各位点基因型及等位基因频率的差异.结果 CAD组中eNOS基因-786T/C位点CC基因型频率为2.0%,4a4b位点4a/4a基因型频率为5.4%,对照组eNOS基因-786T/C位点CC基因型频率为0.0%,4a4b位点4a/4a基因型频率为0.9%,差异有统计学意义(P＜0.05).CAD组和对照组在eNOS基因的894G/T位点等位基因和基因型频率分布差异均无统计学意义(P＞0.05).结论 eNOS基因-786T/C和4a4b多态性与中国汉族人群CAD存在关联,C等位基因和4a等位基因可能是CAD发病的危险因素.eNOS基因894G/T位点与CAD发病无明显相关.

Abstract：

Objective To investigate the relationship between the 3 polymorphisms ( -786T/C,4a4b,894G/T) in endothelial nitric oxide synthase (eNOS) gene and coronary artery disease (CAD).Methods 146 patients with CAD and 113 healthy unrelated individuals in a Chinese Han nation were involved.The genotype and allele frequency of each polymorphism of the eNOS gene in these patients and normal controls were examined by using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or PCR methods.Genotypes and allele frequency were analyzed by HaploView 4.0 and SPSS13.0 software.Results The frequency of CC genotype of the -786T/C was 2.0%,and that of 4a/4a genotype of the 4a4b was 5.4% in CAD.The frequency of CC genotype of the - 786T/C was 0.0%,and that of 4a/4a genotype of the 4a4b was 0.9% in controls ( P＜0.05 ).There were significant differences in both allele and genotype frequency of -786T/C and 4a4b between CDA group and control group.Between patients with CAD and controls,there were no significant differences in the frequency of the genotypes and alleles of the 894G/T in eNOS gene.Conclusion The - 786T/C and 4a4b polymorphisms of eNOS gene may be associated with CAD.The individuals with C allele of - 786T/C and 4a allele of 4a4b are susceptible to CAD.There is no significant correlation between 894G/T polymorphism in eNOS gene and CAD.     

中国南方汉族散发性激素耐药型肾病综合征儿童NPHS1基因突变分析

目的 研究我国南方汉族散发性激素耐药型肾病综合征(SRNS)儿童NPHS1基 因突变情况.方法 对象为40例南方汉族散发性SRNS儿童,50例尿检正常的汉族健康成年人作为对照.取受检者外周静脉血3ml,10％枸橼酸钠抗凝,提取基因组DNA.应用PCR方法扩增NPHS1基因全部29个外显子及其周围的部分内含子,对PCR产物直接进行DNA序列测定及突变分析.结果 6例存在NPHS1基因突变-928G ＞A (D310N)、2677A ＞G( T893A)、2869G＞C( V957L)、IVS8+30C＞T、IVS21+ 14G＞A、IVS25-23C ＞T和*142T＞C,突变检出率为15％.在50例健康对照人群中未检测出这7个变异,其中2677A ＞G、IVS8 +30C ＞T、IVS21+ 14G＞A、IVS25-23C＞T和*142T＞C为新发现NPHS1基因突变.此外,还确定了13个已报道的NPHS1基因多态性-294C ＞T、349G ＞A、IVS3+ 15C ＞T、IVS3 +61A ＞G、803G ＞A、IVS8+68A ＞G、1339G ＞A、1802G ＞C、2223C ＞T、2289C ＞T、IVS24 +36C ＞T、3315G＞A和IVS27 +45C ＞T.结论 在40例南方汉族散发性SRNS患儿中,NPHS1基因突变检出率为15％,提示南方汉族散发性SRNS患儿存在NPHS1基因突变,对这类患儿需进行NPHS1基因突变分析.     

膀胱癌易感性与巨噬细胞移动抑制因子基因-173G＞C多态性位点的关系

目的 探讨巨噬细胞移动抑制因子(MIF)基因-173G＞C位点多态性与中国南方汉族人群膀胱癌的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测年龄和性别匹配的中国南方汉族217例膀胱癌患者和249例正常人群的MIF-173G＞C基因型.通过分层分析探讨年龄、性别、吸烟和饮酒对罹患膀胱癌的影响.结果 与-173GG比较,携带MIF-173G/CC基因型者可降低罹患膀胱癌的危险性(OR=0.63,95%CI=0.43～0.93).分层分析结果 显示,年龄大(＞55岁)的男性在吸烟和饮酒下携带-173GC/CC基因型具有保护作用(年龄＞55岁:OR=0.58,95%CI=0.38～0.89;男性:0.51、0.33～0.78;吸烟:0.50、0.29～0.86;饮酒:0.40、0.23～0.70).结论 MIF-173G＞C多态性可能与我国汉族人群膀胱癌发生有关.     

Association of XRCC1 gene polymorphisms with idiopathic azoospermia in a Chinese population

Aim： To assess the possible role of genetic polymorphisms in DNA repair gene XRCC 1 （X-ray repair cross-comple- menting group l） during spermatogenesis by investigating the associations of one promoter polymorphism （T-77C） and two exonic polymorphisms （Argl94Trp and Arg399Gln） in XRCC1 gene with risk of idiopathic azoospermia in a Chinese population. Methods： The genotype and allele frequencies of three observed polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia subjects and 247 normal-spermatogenesis controls. Results： In our study, all the observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium. The 399A （GA＋AA） allele frequency for idiopathic azoospermia subjects and controls was 0.216 and 0.269, respectively. Compared with GG genotype, the AA genotype of Arg399Gln showed a significant association with a decreased risk of idiopathic azoospermia （odds ratio = 0.315; 95% confidence interval = 0.12-0.86）. However, no significant differences were found between the cases and controls for T-77C and Arg194Trp polymorphisms. The major haplotypes of XRCC1 gene were TCG, TrG and TCA, whereas no haplotypes appeared to be significantly associated with idiopathic azoospermia based on the cutoff of P 〈 0.05. Conclusion： In a selected Chinese population, AA genotype of Arg399Gln appears to contribute to a decreased risk of idiopathic azoospermia, while we have not any evidence of involvement of XRCC1 T-77C and Arg194Trp polymorphisms in idiopathic azoospermia. （Asian J Androl 2007 Nov; 9： 843-848）     

有机阴离子转运体1B1和1B3基因多态性对肾移植受者血麦考酚酸浓度的影响

目的 探讨有机阴离子转运体1B1和1B3(编码基因分别为SLCO1B1和SLCO1B3)基因多态性对肾移植受者血麦考酚酸(MPA)浓度的影响.方法 用聚合酶链反应-连接酶检测反应法对68例汉族肾移植受者的SLCO1B1和1B3基因进行单核苷酸基因多态性(SNP)检测,分别检测SLCO1B3 T334G和SLCO1B1 A338G的突变位点.术后第28天,收集受者血浆检测MPA浓度.比较各基因型受者的MPA浓度-时间曲线下面积(AUC0-12),分析单核苷酸多态性与MPA AUC0-12之间的相关性.结果 SLCO1B3 T334G位点GG基因型受者的MPA AUG0-12高于TT基因型受者,分别为(54.54±14.40)mg·h·L-1和(37.30±12.88)mg·h·L-1(P=0.052);SLCO1B1 A338G位点的各个基因型受者之间MPA AUC0-12比较,差异均无统计学意义(P>0.05).结论 SLCO1B3基因多态性对肾移植受者术后血MPA浓度的个体间差异产生明显影响.

Abstract：

Objective To analyze the relationship between the genetic polymorphisms of organic anion transporting polypeptide (SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA)pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations (SLCO1B3T334G, SLCO1B1 A338G) were detected in 68 recipients by PCR-LDR. The plasma samples were collected and blood concentration of MPA was measured on the 28 th day after transplantation. The area under the curve (AUC)0-12 of MPA in different genotype recipients was compared to analyze the correlation between single nucleotide polymorphisms (SNPs) and MPA pharmacokinetics. Results MPA AUC0-12 was higher in SLCO1B3 T334G GG carriers group than in TT carriers [(54. 54 ±14.40)vs(37.30±12.88)mg·h·L-1,(P=0.052)].However,there was no difference in MPA AUC0-12 among each genotype of SLCO1B1 A338G (P>0. 05). Conclusion Genetic polymorphisms of SLCO1B3 affect interindividual variety in plasma MPA concentration in Chinese kidney transplantation recipients.     

细胞色素P450氧化酶3A4*1G基因多态性对新疆维吾尔族与汉族患者芬太尼术后镇痛效应的影响

目的 研究细胞色素P450氧化酶(cytochrome P450 enzyme,CYP)3A4*1G在新疆维吾尔族及汉族人群的分布特征及其与芬太尼术后镇痛的用量及效果的关系. 方法 选择美国麻醉医师协会(ASA)分级Ⅰ或Ⅱ级,在全身麻醉下行择期妇科手术的患者71例,按民族分为2组:维吾尔族组(U组)37例和汉族组(H组)34例.采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术进行CYP3A4* 1G基因多态性检测,统计其等位基因和基因型频率.术后采用芬太尼患者静脉自控镇痛(patient controlled intravenous analgesia,PCIA),记录并比较两组间术后6、24、48 h的视觉模拟评分(visual analogue scale,VAS)、Ramasay镇静评分、生命体征、48 h内患者PCIA芬太尼总用量. 结果 ①U组患者中GG、GA、AA基因型分布频率分别为86.5％、10.8％和2.7％,H组患者中GG、GA、AA基因型分布频率分别为50.0％、44.1％和5.9％;U组患者G等位基因和A等位基因分布频率分别为91.9％和8.1％,H组患者分别为72.1％和27.9％;两组间基因型分布频率和等位基因分布频率差异均有统计学意义(P＜0.05).②两组患者各时点(术后6、24、48 h)脉搏血氧饱和度(pluse oxygen saturation,Sp02)、Ramasay镇静评分和VAS评分比较差异均无统计学意义.③U组PCIA 48 h内芬太尼总用量明显多于H组(P＜0.05);U组和H组CYP3A4*1G突变型(GA型+AA型)PCIA 48h内芬太尼总用量明显低于野生型(GG型)(P＜0.05). 结论 CYP3A4*1G基因多态性分布在新疆维吾尔族和汉族患者之间存在差异,此差异可能是两民族患者之间芬太尼术后镇痛效应出现差异的主要因素.     

先天性巨结肠与RET基因多态性和单倍型的关系

目的 研究先天性巨结肠与RET基因多态性的关系,进一步推断主要的先天性巨结肠相关单倍型,并分析浙江汉族人群RET基因单核苷酸多态性的分布特点.方法 采集2005年至2007年浙江大学医学院附属儿童医院收治的123例汉族先天性巨结肠患儿以及194例健康体检儿童的外周血,并提取DNA.根据选取的RET基因单核苷酸多态性合成引物,行PCR扩增,经2%琼脂糖电泳证实PCR产物后,将PCR产物进一步纯化、测序.采用PHASE软件计算单倍型频率.将健康儿童RET基因各位点等位基因频率与文献和数据库已有的其他种族资料进行比较.RET基因和先天性巨结肠间关系的分析采用x2检验,以比值比及95%可信区间表示.结果 RET基因-5G＞A、-1A＞C、c135G＞A、c2307T＞G 4个位点的少见基因型AA、CC、AA、GG在先天性巨结肠患儿中的频率显著高于健康儿童(x2=57.775,20.469,57.040,38.869,P＜0.05).RET基因-5A、-1C、c135A、c2307G在先天性巨结肠患儿中等位基因频率显著高于健康儿童(x2=85.114,53.117,77.005,70.161,P＜0.05).RET基因各位点等位基因频率在不同类型先天性巨结肠间的差异无统计学意义(x2=0.048,0.265,0.395,0.027,P＞0.05).RET基因4个位点单倍型中ACAG占先天性巨结肠患儿的75.2%,显著高于健康儿童的38.7%(x2=62.776,P＜0.05).本组健康儿童RET基因-5A、c135A和c2307G位点的少见等位基因频率明显高于欧洲高加索人和非洲约鲁巴人(P＜0.05).结论 RET基因-5G＞A、-1A＞C、c135G＞A、c2307T＞G 4个位点多态性与浙江汉族人群先天性巨结肠发病明显相关,但与先天性巨结肠类型无关.RET基因4个位点单倍型中ACAG是浙江汉族人群的先天性巨结肠相关核心单倍型.浙江汉族人群的RET基因-5、c135和c2307位点的少见等位基因频率显著高于欧洲高加索人和非洲约鲁巴人.     

瘦素基因启动子区-2548 G/A多态性与胆囊胆固醇结石的相关性分析

目的探讨瘦素基因启动子区-2548 G/A功能多态性与胆囊胆固醇结石之间的相关性。方法采用聚合酶链反应-限制性片段长度多态性技术对118例胆囊结石患者和53例正常对照人群进行瘦素基因启动子区-2548 G/A基因多态性分析,研究等位基因和基因型分布规律。结果瘦素基因启动子区-2548 G/A多态性在2组中的分布差异有统计学意义,胆囊结石组中AA+GA基因型频率明显高于对照组(2χ=4.251,P=0.039),AA+AG基因型患胆囊结石的风险是GG基因型的2.813倍(OR=2.813,95%CI=1.020～7.757)。等位基因频率在2组中分布也存在差异,胆囊结石组A等位基因频率明显高于对照组(2χ=5.791,P=0.016),A等位基因携带者患胆囊结石的风险是G等位基因携带者的1.777倍(OR=1.777,95%CI=1.110～2.844)。结论瘦素基因启动子区-2548 G/A功能多态性与胆囊结石易感性有关,A等位基因是胆囊结石发病的遗传易感基因,G等位基因是胆囊结石的保护基因。     

μ阿片受体A118G基因多态性对妇科手术患者疼痛敏感性的影响

目的 μ阿片受体A118G基因(OPRM1 A118G基因)多态性对妇科手术患者电刺激痛敏感性的影响.方法 择期拟行子宫肌瘤剔除术或子宫全切术患者152例,汉族,年龄20～50岁,体重指数19～21 kg/m~2,ASA Ⅰ或Ⅱ级,根据基因型分为野生型纯合子组(A/A组)、突变型杂合子组(A/G组)和突变型纯合子组(G/G组).采用电刺激测定患者痛阈和耐痛阈.使用聚合酶链反应-限制性片段长度多态性技术检测OPRM1 A118G基因多态性.结果 A/A组76例,A/G组56例,G/G组20例;G等位基因频率为31.6%.三组间痛阈差异无统计学意义(P＞0.05);G/G组耐痛阚低于A/A组和A/G组(P＜0.05);A/A组和A/G组耐痛阈差异无统计学意义(P＞0.05).结论 OPRM1 A118G基因突变可导致妇科手术患者耐痛阈降低,对痛阈无影响.     

c.822＋126T〉G/C：a novel triallelic polymorphism of the TSSK6 gene associated with spermatogenic impairment in a Chinese population

TSSK6 is a member of the testis-specific serine/threonine kinase family. Male Tssk6 knockout mice are infertile owing to sperrnatogenic impairment,including sperm count reduction,a decrease in motile sperm number and motility rates,and an increase in the number of sperms with abnormal morphology. We investigated the possible association between variations oftbe TSSK6 gene and spermatogenic impairment in humans. Mutation screening of TSSK6 was carried out in 519 patients with azoospermia （n = 273） or severe oligozoospermia （n = 246） and in 359 controls with normozoospermia by denaturing high-performance liquid chromatography and DNA sequencing. The frequencies of alleles and genotypes of gene polymorphism were compared between patients and controls. A novel triallelic polymorphism in TSSK6,c.822＋126T〉G/C,was identified. The frequencies of genotype TT and allele T were increased dramatically in infertile patients compared with controls,whereas genotype TG,allele G and allele C frequencies were significantly higher in controls than in patients. Further study revealed that the allele C frequency of controls was remarkably higher than that of patients with oligospermia. Our findings,for the first time,suggested an association of c.822＋I26T〉G/C in TSSK6 with spermatogenic impairment in humans in which allele T may be a risk factor for male infertility,while alleles C and G may decrease susceptibility to male infertility.     

Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A preliminary study

AIM To assess circulatory levels of interleukin-18(IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODS This study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight(18.0-22.9 kg/m~2), overweight(23.0-25.9 kg/m~2) and obese( 26.0 kg/m~2) according to South Asian criteria of BMI. Fasting blood glucose(FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor(TNF)α were measured using ELISA kits, whereas low density lipoprotein(LDL)-cholesterol, insulin resistance(HOMA-IR) and insulin sensitivity(QUICKI) were calculated. The body fat percentage(BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18-607 C/A polymorphism was performed by using tetraprimer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson's χ~2 test and Pearson's correlation were used, where a P value 0.05 was considered significant.RESULTS In an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight(P 0.001).Highest levels of IL-18 and TNF levels were also seen in obese subjects(IL-18: 58.87 ± 8.59 ng/L)(TNF: 4581.93 ± 2132.05 pg/m L). The percentage of IL-18-607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects(P 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC(heterozygous) or CC(wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. CONCLUSION This preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop Met S. Further studies are required to validate our findings.     

云南省德宏州傣族和汉族志愿者细胞色素P450 1A2~* 1C基因的多态性

目的 探讨傣族和汉族志愿者细胞色素P450 1A2~*1C(CYP1A2~*1C)基因的多态性.方法 云南省德宏州117名傣族志愿者和112名汉族志愿者纳入本研究.应用聚合酶链反应-限制性片段长度多态性的方法进行CYP1A2-2964位点分型,检测CYP1A2-2964位点的基因多态性.结果 云南省德宏州117名傣族志愿者中,45名为野生型纯合子(G/G);63名为杂合子(G/A);9名为突变型纯合子(A/A);112名汉族志愿者中,63名为野生型纯合子(G/G);44名为杂合子(G/A);5名为突变型纯合子(A/A),傣族与汉族志愿者G-2964A基因型分布差异有统计学意义(P<0.05);G-2964A基因频率经检验分布符合H-W平衡定律;德宏州傣族和汉族志愿者A-2964位点等位基因频率分别为35%(95%可信区间30%～40%)和24%(95%可信区间20%～30%),傣族和汉族志愿者间差异有统计学意义(P<0.05);云南省德宏州傣族志愿者A-2964等位基因频率与其他地区人群比较差异有统计学意义(P<0.05).结论 在云南省德宏州CYP1A2~*1C基因多态性是引起傣族和汉族人药理学特性个体和种族差异的遗传因素之一.     

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

Glutathione S-transferases （GSTs）, superoxide dismutase 2 （SOD2） and NAD（P）H：quinone oxidoreductase 1 （NQO1） are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase 7：1 （GSTT1）-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction （PCR）. Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism （PCR-RFLP） method. A significantly better response to varicocelectomy was found in patients with the GSTTI-wt genotype （63.2%） and NQO1-Ser/Ser genotype （80.0%） than in those with GSTTI-null genotype （35.3%） and NQO1-Pro/Pro or NQO1- Pro/Ser genotype （45.2%）, respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.     

腰椎间盘退变性疾病与COL9A2基因多态性的关系

目的 探讨COL9A2基因多态性与腰椎间盘退变性疾病(DDD)的关系.方法 采用"病例-对照"研究方法:125例中国汉族DDD患者(DDD+)与126例中国汉族非DDD受访者(DDD-),用SNP分型系统-SNPstream UIT(Cenotyping System)对所有样本的所选SNP位点行基因型鉴定.对检测数据分别行拟和优度x2检验、基于等位基因频率/基因型的关联分析.结果 共筛查SNPl(rs12722877)、SNP2(rs3737820)、SNP3(rs209914)和SNP4(rs6676013)4个位点.病例组中和对照组中,两个位点的基因型分布均符合Hardy-Weinberg平衡;病例/对照组中等位基因频率分别为:SNP1C=228(91%)/22(9%)、SNP1G=235(93%)/17(7%),SNP2A=214(86%)/36(14%)、SNP2T=223(89%)/27(11%),SNP3A=237(95%)/13(5%)、SNP3C=238(94%)/14(6%),SNP4C=30(12%)/220(88%)、SNP4T=26(10%)/226(90%),差异无统计学意义(P＞0.05).病例/对照组中基因型频率差异无统计学意义(P＞0.05).结论 COL9A2基因可能不是决定中国汉族人群腰椎DDD的主要危险因素.

Abstract：

Objective To investigate the association between COL9A2 gene polymorphism with lumbar degenerative disc disease (DDD) in Chinese Han population. Methods A total of 125 DDD patients (58 males and 67 femals, aged 51.8 + 10. 6), and 126 controls matched in sex and age (64 males,62 femals, aged 45.7 + 8. 2) were recruited in the case-control study. Peripheral blood was collected for DNA isolation. Results Based on NCBI Genebank, corresponding single nucleotide polymorphisms-SNP1 ( rs12722877), SNP2 ( rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were identified. Hardy-Weinberg equilibrium was analyzed in both case and control groups. Genotying of all selected SNPs was done by SNPstream technology. The association analysis between phenotyepes and SNPs was conducted.Reslults NPI (rs12722877), SNP2 (rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were genttyped, and the polymorphisms distributed in line with Hardy-Weinberg equilibrium in case and contral groups. There was no significant difference in allele frequency of SNP1C, SNPIG, SNP2A, SNP2T,SNP3A, SNP3C, SNP4C and SNP4T between case group (91%, 93%, 86%, 89%, 95%, 94%, 12%,and 10%, respectively) and control group (9%, 7%, 14%, 11%, 5%, 6%, 88%, and 90% respectively). No significant difference in genotype frequencies of SNP was found between case group and control group, too (all P＞0.05). Conclusion COL9A2 gene may not be associated with lumbar DDD in ChineseHan population.