CRELD1基因多态性与新疆维吾尔族先天性心脏病相关性研究

目的研究CRELD1基因单核苷酸多态性与新疆维吾尔族先天性心脏病的关系。方法选择112例新疆维吾尔族先天性心脏病患者和112例年龄、性别匹配的对照者。选择CRELD1基因的6个SNPs(rs3894571、rs3846167、rs2302785、rs279552、rs17050660、rs279551),应用TaqMan SNP基因分型的方法进行基因分型,分析CRELD1基因单核苷酸多态性与新疆维吾尔族先天性心脏病的相关性。结果患者年龄和性别在入选样本时进行了匹配,所以在分析时进行了剔除。对先心病患者母亲的年龄、文化程度、忧虑情绪、饮食状况等基本情况进行单因素分析,结果显示年龄、文化程度、忧虑情绪、饮食状况等因素与先心病发生有关联。病例组与对照组CC、CT及TT基因型频率分别为74.35%、22.28%、3.37%和83.03%、16.07%、0.90%,两组比较无统计学差异(χ2=5.488,P>0.05)。两组均以CC型为主,等位基因以C占优势,病例组TT基因型频率高于对照组,但是差异无统计学意义(P>0.05),而CT、CT+TT基因型频率和携带T等位基因频率高于对照组,有统计学意义(P<0.05)。应用Logistic回归分析先心病主要相关因素:母亲年龄、文化程度、忧虑情绪、饮食状况对结果的影响,rs3894571 CT、CT+TT、CT、等位基因T因素进入回归方程。结论 CRELD1基因核苷酸多态性与新疆维吾尔族先天性心脏病有相关性。     

ADAM 33 基因 S1、 S2 位点单核苷酸多态性与新疆维吾尔族 COPD 易感性的关系

目的 探讨 ADAM 33 基因 S1、 S2 位点单核苷酸多态性（SNP）与中国新疆维吾尔族慢性阻塞性肺疾病（COPD） 患者易感性的关系。方法 收集 217 例 COPD 患者 （病例组） 和 218 例健康对照者 （对照组） 外周血标本, 提取标本 DNA, 采用美国生物应用系统公司(ABI)SNaPshot SNP 分型技术检测 ADAM 33 基因 S1、 S2 位点单核苷酸多态性。结果 病例组和对照组 S1 位点 CC、 CT、 TT 3 种基因型分布和 C、 T 等位基因分布频率比较差异无统计学意义;S2 位点 CC、 CG、 GG 3 种基因型分布和 C、 G 等位基因分布频率比较差异无统计学意义。病例组 S1、 S2 位点基因型与肺功能相关临床指标的关系显示： S1、 S2 位点 3 种基因型第 1 秒用力呼气容积（FEV1）预计值（%）比较、 FEV1/用力肺活量 （FVC） 比较差异无统计学意义。单体型分析结果显示 3 种单体型在病例组和对照组中比较差异无统计学意义。结论 ADAM 33 基因 S1、 S2 位点 SNPs 与新疆维吾尔族人群COPD 患者易感性无明显相关性。     

ABCA1基因单核苷酸多态性的临床意义

ATP结合的盒转运子A1(ATP Banding cassette Transporter al，ABCA1)促进细胞内游离胆固醇和磷脂的流出，在胆固醇逆转运(RCT)和HDL生成的起始步骤起重要作用；同时ABCA1与动脉粥样硬化(AS)和冠心病的发生密切相关。ABCA1基因的单核苷酸多态性(SNP)广泛存在于普通人群及冠心病人群中，不同人种、不同SNP位点对ABCA1功能影响不同，同一SNP在不同人种其作用也不同，ABCAISNP与血浆HDL—C水平、炎症细胞因子及冠心病发生密切相关。因此，ABCAISNP可能是影响血浆HDL—C水平及冠心病发生的重要因素。     

贵州省水族人群XRCC1基因单核苷酸多态性及其组合型研究

目的 分析水族人群DNA修复基因XRCC1 C26304T、G27466A与G28152A单核苷酸多态性及其等位基因频率与组合分布特征.方法 获取自然人群个体水族197例血白细胞基因组DNA,利用PCR扩增限制性酶切法(PCR-RFLP)检测XRCC1 C26304T、G27466A与G28152ASNPs.结果 XRCC1 C26304T SNPs基因型分布CC、CT、TT分别为57.4%、33.5%、9.1%,C、T等位基因频率分别为74.1%、25.9%.XRCC1 G27466A SNPs基因型分布GG、GA、AA分别为79.7%、18.9%、1.5%,G、A等位基因频率分别为89.1%、10.9%.XRCC1 G28152 A SNPs基因型分布GG、GA、AA分别为49.2%、43.7%、7.1%,G、A等住基因频率分别为71.1%、28.9%.XRCC1基因在C26304T和G28152A两位点的SNPs组合基因型频率较高的为CC GA 53例(26.9%);C26304T和G274 66A两位点的SNPs组合基因型频率较高的为CC GG 84例(42.6%);G28152A和G27466 A两位点的SNPs组合基因型频率较高的为GA GG 73例(37.1%).结论 本研究揭示了水族人群XRCC1基因3位点的单核苷酸多态性、基因型及其组合分布特征,为进一步研究该基因SNPs与其生理功能和疾病的关系提供基础资料.     

新疆维吾尔族健康人群细胞色素P450基因多态性研究

目的了解CYP2C9基因多态性在新疆维吾尔族健康人群中的分布以及与其他不同民族之间的差异。方法采用序列特异性引物聚合酶链反应和限制性内切酶反应(PCR-RFLP)技术对197名乌鲁木齐地区维吾尔族健康个体CYP2C9*2和CYP2C9*3位点进行了检测,计算其基因型和等位基因频率,并与国外多个民族CYP2C9基因多态性分布进行比较。结果国内首次在新疆维吾尔族健康人群中发现CYP2C9*2等位基因,新疆维吾尔族健康人群中共检测到3种等位基因:CYP2C9*1、CYP2C9*2、CYP2C9*3,等位基因频率分别为80%、3%、17%。新疆维吾尔族健康人群CYP2C9共检测到5种基因型,以CYP2C9*1*1常见,基因型频率为77%,其次为CYP2C9*3*3,基因型频率为15%。CYP2C9*1*2、CYP2C9*1*3和CYP2C9*2*2的基因型频率分别为4%、3%和1%。结论新疆维吾尔族CYP2C9基因多态性的分布与欧美人群接近,而与日本、韩国以及国内报道的汉族人群CYP2C9基因多态性分布有较大差异。     

新疆多民族UGT1A9基因多态性与丙泊酚血药浓度相关性

目的:探讨新疆多民族患者尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A9基因多态性与丙泊酚血药浓度的相关性。方法:选取2019年12月至2021年3月新疆医科大学附属肿瘤医院102例多民族患者,采用气-质联用(LC-MS)法检测患者5个时间点,即麻醉诱导前(T₀)、睫毛反射消失前(T₁)、血浆清除率至40～50 L·kg^-1·h^-1时(T₂)、停药即刻(T₃)和停药后30 min时(T₄)外周血中丙泊酚的血药浓度。同时提取患者外周血DNA,采用基质辅助激光解吸电离飞行时间质谱(MAL-DI-TOF-MS)法检测对UGT1A9(rs 2741049、rs 3806598、rs 6731242、rs 3832043)4个基因位点进行基因多态性检测。统计基因分型结果,将影响血药浓度的所有因素进行单因素分析。结果:rs 2741049,rs 3806598,rs 6731242,rs 3832043四个位点基因型频率均符合Hardy-Weinber...     

系统性红斑狼疮易感基因单核苷酸多态性研究进展

系统性红斑狼疮(SLE)是临床上常见的自身免疫性疾病，其发病机制还不清楚，在其发病机理上，遗传和环境因素都起关键作用，但一般认为环境因素仅在一定的遗传背景下触发疾病。随着人类基因组计划的迅速发展及新的分析技术的应用，SLE遗传学研究有了很大的进展。近年来大量研究显示SLE具有很强的遗传倾向，其同胞患病率／一般人患病率(λs)达20，同卵双生子发病一致率为24％～65％，而异卵双生子发病一致率仅2％～9％。     

中国健康汉族和维吾尔族人谷胱甘肽硫转移酶的基因多态性

目的 比较中国健康汉族人和维吾尔族人GSTM1、GSTT1和GSTP1基因多态性分布。方法 用多重PCR分析GSTM1和GSTT1基因多态性，PCR—RFLP检测GSTP15号外显子105位密码子基因多态性。结果 汉族人与维吾尔族人的GSTM1纯合缺失频率接近。分别为56.1％和53.2％。而汉族人的GSTT1纯合缺失频率（50．0％）较维吾尔族人（26．6％）高。汉族人GSTP1 105I／I、I／V和V／V基因型频率分别为60．7％，35．2％和4．1％；维吾尔族人分别为51．3％，40．2％and 8．4％。结论 维吾尔族人与汉族人，除GSTM1外，GSTT1与GSTP1突变基因型频率存在明显种族差异。     

CYP1A1基因多态性与宫颈癌遗传易感性的关系

目的 探讨CYP1A1基因Exon7位点和Msp1位点多态性与宫颈癌遗传易感性的关系.方法 280例老年官颈癌患者为实验组,280例健康体检者为对照组,用CR-RELP技术和ASAPCR技术分别检测两组人群Msp1位点和Exon7位点的多态性.结果 两组在CYP1A1Ⅱe/Val位点分布上差异有统计学意义(P＜0.05);且携带Ⅱe/Val基因型的个体发生官颈癌的危险是携带Ⅱe/Ⅱe基因型个体的2.473倍.而两组的Mspl基因型多态性分布频率及OR值均无统计学差异(P＞0.05).结论 CYP1A1 Exon7基因多态性是发生宫颈癌的危险因素,有可能成为宫颈癌遗传易感标记物.Mspl位点多态性与官颈癌易感性可能无关.     

HMG-CoA还原酶基因单核苷酸多态性与冠心病的关联研究

目的探讨3-羟-3-甲基戊二酰辅酶A(3-hydroxy-3-methylglutaryl coenzyme A,HMG-CoA)还原酶基因的BsuR I和ScrF I等2个限制性内切酶多态位点各等位基因与冠心病(CHD)易感性和冠心病患者血脂水平变化之间的关系。方法PCR扩增203例CHD患者和100例对照的2个多态位点相应的DNA片段,经限制性内切酶消化并电泳后确定基因型,用SPSS软件进行统计学分析。结果2个多态位点的等位基因频率和基因型频率在CHD患者组和对照组间无显著差异。ScrF I多态位点AA基因型的CHD患者其TC和LDL-C水平比aa基因型的CHD患者显著增高(P=0.031;P=0.028),且TC/HDL-C比值比较也有统计学意义(P=0.039)。结论ScrF I多态位点的A等位基因与CHD患者较高的TC和LDL-C水平以及较高的TC/HDL-C比值相关联,此点在寻找CHD的危险因素和易感个体的筛查等方面可能具有一定的参考意义。     

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin

Aim:

To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM).

Methods:

The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzyme-electrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured.

Results:

The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29±0.45 mmol/L vs 1.18±0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18±0.15 vs 1.04±0.27 mmol/L, P=0.008) and GG genotypes (1.40±0.51 vs 1.19±0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group.

Conclusion:

There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.     

Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene

The gene encoding the human muscarinic receptor, type 1 (CHRM1), was genotyped from 245 samples of the Coriell Collection (Coriell Institute for Medical Research, Camden, NJ). Fifteen single nucleotide polymorphisms (SNPs) were discovered, 9 of which are located in the coding region of the receptor. Of these, 8 represent synonymous SNPs, indicating that CHRM1 is highly conserved in humans. Only a single allele was found to contain a nonsynonymous SNP, which encodes an amino acid change of Cys to Arg at position 417. This may have functional consequences because a C417S point mutation in rat M1 was previously shown to affect receptor binding and coupling. Furthermore, 0 of 4 SNPs within CHRM1 previously deduced from sequencing of the human genome were found in this study despite a prediction that a majority of such inferred SNPs are accurate. The consensus sequence of CHRM1 obtained in our study differs from the deposited reference sequence (AC NM_000738) in 2 adjacent nucleotides, leading to a V173M change, suggesting a sequencing error in the reference sequence. The extraordinary sequence conservation of the CHRM1 gene-coding region was unexpected as M1-knockout mice show only minimal functional impairments.     

多药耐药基因MDR1多态性的研究进展

MDR1所编码的P-糖蛋白是ABC蛋白家族成员之一,它在体内药物的转运和处置中发挥着重要作用。本文就近几年有关MDR1基因多态性对P-糖蛋白在组织中表达的影响、以及MDR1多态性对药物处置、临床疗效以及疾病风险等影响进行综述。     

Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population

Aim:

Genome-wide association studies have identified several novel loci associated with serum uric acid concentrations in individuals of European descent. In the current study, we aimed to evaluate the associations between these loci and serum uric acid concentrations in a Chinese population.

Methods:

Fourteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped in 2329 Chinese subjects in Shanghai. Serum biochemical parameters including uric acid concentrations were determined. All the variants were analyzed for gender differences since uric acid metabolism differed between genders.

Results

In males after adjustments for age and BMI, GCKR rs780094, SLC2A9 rs11722228 and SF1 rs606458 were associated with the uric acid concentrations, which were statistically significant (P=0.016, 0.001 and 0.03, respectively), whereas SLC2A9 rs3775948 was marginally associated with the uric acid concentrations (P=0.071). In females, SLC22A12 rs506338 was also marginally associated with the uric acid concentrations (P=0.057). The meta-analysis for combined data from both males and females revealed that rs3775948 and rs606458 were associated with the uric acid concentrations (P=0.036 and 0.043, respectively). Furthermore, the gender significantly affected the association of rs11722228 with serum uric acid levels (P=0.012).

Conclusion

The SLC2A9 rs11722228, SF1 rs606458 and GCKR rs780094 variants modulate uric acid concentrations in Chinese males, while SF1 rs606458 and SLC2A9 rs3775948 are associated with the uric acid concentrations in both Chinese males and females.     

Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms

We analyzed the functional properties of five nonsynonymous single nucleotide polymorphisms (SNPs) in the sodium-phosphate transporter NPT4 gene (SLC17A3) using the Xenopus oocyte expression system. NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [(14)C]para-aminohippurate, [(3)H]bumetanide, [(3)H]estrone sulfate, and [(14)C]urate, when each variant clone was expressed in the plasma membrane of oocytes. This study suggests the possibility that the genetic variation of NPT4 contributes to inter-individual differences in disposition of anionic drugs such as diuretics as well as certain endogenous organic anions such as urate.     

中国汉族人孕烷X受体基因NR1I2的单核苷酸多态性

目的了解中国健康汉族人孕烷X受体基因NR1I2的单核苷酸多态性分布以明确种族差异。方法用PCR扩增后直接测序的方法,检测NR1I2基因2和4外显子及1,2,4和5内含子的单核苷酸突变。结果中国健康汉族人NR1I2基因2和4外显子均未发现已报道的单核苷酸突变,外显子1和内含子1,2,4和5检测到单核苷酸突变9种,分别为-24446C>A,-24381A>C,-24113G>A,252A>G,275A>G,4760G>A,7635G>A,7637C>T和7675C>T,等位基因频率分别为2.4%,20.8%,20.8%,33.3%,31.0%,68.5%,31.7%,1.6%和10.6%,其中7637C>T未见在任何文献和单核苷酸多态性数据库中报道,为新发现突变。结论中国健康汉族人NR1I2内含子1,2,4和5位置检测到9种单核苷酸突变,且突变频率较高,与白人和美国黑人比较,单核苷酸突变的发生位点和发生频率存在显著性差异。     

Association study on GNB3 gene polymorphism with essential hypertension in Xinjiang Uygur group

The relationship between the tenth exon C825T of G-protein β3 subunit (GNB₃) genetic polymorphism and hypertension in the Uygur population of China was investigated. A nested case-control study (n = 738) was carried out. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to genotype GNB₃ C825T polymorphism in 354 hypertensive (HT) and 384 normotensive (NT) Uygur subjects. The distributions of GNB₃ C825T genotypes were CC (27.2%), TT (42.9%), and CT (29.9%) in the hypertensive subjects and CC (27.7%), TT (42.4%), CT (29.9%) in the normotensive subjects. There were no significant differences in the genotype distributions between the two groups (χ ² = 0.0262 P = 0.99). The T allele was 51.4% in hypertensive subjects and 51.2% in normotensive subjects, which, between the two groups, was not a significant difference (χ ² = 0.0016 P = 0.97). Further analysis shows that there is no association between C825T genotypes and age, body mass index (BMI), Glucose (GLU), Triglyceride (TG), Cholesterol (CHO), systolic blood pressure (SBP) and diastolic blood pressure (DBP). No evidence was found to suggest an association between GNB₃ C825T polymorphism and hypertension in the Uygur population of China. Translated from Journal of Fudan University (Medical Sciences), 2006, 33(4): 433–436 [译自: 复旦大学学报 (医学版)]     

Relationship between the mutation of G239V point in SLC17A3 gene and primary gout

Objective To explore the relationship between the mutation of G239V point in SLC 17A3 gene and primary gout.Methods The single nucleotide polymorphism (SNP) of gene in 530 sporadic patients with primar...     

DIO2及UGT1A1基因多态性与左甲状腺素剂量关系的研究进展

甲状腺功能减退症是由于各种原因所致的甲状腺激素合成和分泌减少或组织利用不足,为最常见的内分泌系统疾病之一.左甲状腺素(levothyroxine,L-T4)是治疗该病的首选药物,但约10％的甲状腺功能减退症患者应用L-T4替代治疗效果不佳.影响L-T4治疗达标的因素除了年龄、合并用药、患者的依从性等外,遗传因素是另一重要因素,如Ⅱ型脱碘酶基因(type 2 deiodinase gene,DIO2)和尿苷二磷酸葡萄糖醛酸转移酶(uridine diphosphate glucuronosyltransferase,UGT)1 A1基因多态性.了解基因多态性与原发性甲状腺功能减退症患者L-T4治疗剂量间的关系,可以进一步改善患者的预后,为临床用药提供参考依据.