江苏汉族正常青少年FBN3基因多态性研究

目的 检测江苏地区正常青少年FBN3基因型的分布情况,建立正常青少年FBN3基因多态性分布谱.方法 应用聚合酶链式反应-限制性片段长度多态性技术(PCR-RFLP)对287名江苏地区汉族健康青少年FBN3基因型进行检测分析.结果 287名青少年中,FBN3基因rs35277492(BsrFI)位点只检测到CC(50名)型,Mspl位点CC、CT、TT基因型分布分别为176(64.47%)、91(33.33%)和6(2.20%),MseI位点Cc、CT、TT基因型分布分别为85(29.62%)、133(46.34%)、69(24.04%),NLAⅢ位点GG、GT、TT基因型分别为101(38.11%)、118(44.53%)、46(17.36%).结论 江苏地区汉族健康青少年FBN3基因四个位点多态性分布男女性别之间趋于一致,与日本人有显著差异.rs35277492、rs35579498位点与NCBI公布的美国黑人基因型有显著差异,而rsl2608849、rs7257948位点与NCBI公布的中国北方人群基因型趋于一致.     

江苏汉族青少年雌激素β受体基因多态性分析

目的 研究江苏地区青少年雌激素β受体(ER β)基因型分布情况.方法 应用聚合酶链反应一限制性片断长度多态性技术(PCR-RFLP)对232名江苏地区汉族健康青少年ER-β基因Rsa I和Alu I酶切位点的多态性进行检测分析.结果 RR,Rr,RR基因型分别为93(40.09%),112(48.28%),27(11.63%),AA,Aa,aa基因型分别为172(74.14%),58(25.0%),2(0.86%);两位点男女性间分布比较未见统计学差异(P>0.05);与其他地区成年国人分布情况比较无明显差异;但Alu I基因型与意大利人群基因分布具有统计学差异(P<0.05);两位点与希腊人群基因分布均具有统计学差异(P<0.05).结论 江苏地区汉族健康青少年ER-β基因型分布男女性之间趋于一致,与文献报道的成年国人差异不明显.但与国外成人分布比较差异明显.     

福建地区汉族健康人群维生素D受体基因TaqI多态性分析

目的了解福建地区汉族健康人群维生素D受体（VDR）基因单核苷酸多态性位点分布特点。方法抽取福建地区汉族健康人79例,采用限制性片段长度多态性聚合酶链反应法（PCR-RFLP）测定VDR基因TaqI酶切位点多态性分布。结果 VDR基因TaqI酶切位点有两种基因型,TT、Tt两种基因型分布频率分别为81.01%、18.99%。T等位基因频率占90.51%,t等位基因频率占9.49%。基因型频率分布符合Hardy-weinberg平衡定律（χ^2=0.87,P〉0.05）,具有群体代表性。结论福建地区汉族健康人群VDR基因TaqI酶切位点多态性的分布与其他地区人群的分布,存在差异,可能为种族差异及环境因素的基因频率发生变化。     

新疆汉族健康人群维生素K环氧化物还原酶亚单位1启动子区1639A/G基因多态性研究

目的了解VKORC1-1639A/G基因多态性在新疆汉族健康人群中的分布及其与其他不同民族之间的差异。方法采用PCR-RFLP技术对205名乌鲁木齐地区汉族体检健康人群VKORC1-1639A/G基因多态性进行检测,计算其基因型和等位基因频率,并与国外多个民族VKORC1-1639A/G基因多态性分布进行比较。结果新疆汉族健康人群中共检测到2种等位基因:A和G。等位基因频率分别为87%和13%。新疆汉族健康人群VKORC1-1639A/G基因多态性共检测到3种基因型,以AA基因型常见,基因型频率74%。其次是AG基因型,基因型频率分别为26%。GG基因型的个体仅检测到1例,基因型频率小于1。结论新疆汉族VKORC1-1639A/G基因多态性以A等位基因和AA基因型常见,新疆汉族VKORC1-1639A/G基因多态性与欧美人群相比存在较大差异。     

佛山市汉族人群HIF1A基因1790(G→A)多态性研究

目的 研究低氧诱导因子-1α基因(HIFlA)第12外显子1790(G→A)单核苷酸多态性在广东佛山市汉族人群中的分布特征.方法 随机选取佛山市汉族健康个体90人的血样,提取白细胞基因组DNA,利用限制性片段长度多态性-聚合酶链反应(restriction fragment length polymor-phism-polymerase chain reaction,RFlP-PCR)技术检测HIFlA基因第12外显子1790(G→A)的单核苷酸多态性基因型,并分析其基因多态性特征.结果 HIF1A基因1790(G→A)单核苷酸多态性的GG、GA和AA基因型频率分别为75.56%、21.11%和3.33%,G、A等位基因频率分别为86.11%、13.89%.广东佛山汉族人群HIF1A基因1790(G→A)单核苷酸多态性等位基因分布频率与日本人群相比差异有显著意义(P<0.05).结论 广东佛山汉族人群HIF1A基因1790(G→A)多态性以GG基因型分布频率高,具有一定的种族差异性.     

维生素D受体和雌激素受体基因多态性与骨密度关系的研究

目的：调查维生素D受体（VDR）和雌激素受体（ER）基因多态性在我国人群中的分布,研究基因多态性与骨密度的关系。方法：采用聚合酶链反应和酶切技术,检测131例健康妇女VDR和ER的基因多态性,同时用双能X骨密度仪检测其腰椎骨密度。结果：发现VDR基因型分布频率为BB3．21％,Bb8.4%,bb88.5%;ER基因在健康人群的分布频率为PP16．0％Pp40.4%,pp433.5%;XX1.5%,Xx26.75.xx71.8%。围绝经期妇女VDR基因型Bb型骨密度分别高于BB和bb型,有极显著性差异（P＜0．01）。绝经期妇女腰椎骨密明显低于围绝经期妇女（P＜0．01）。结论：VDR和ER基因型分布频率与西方国家明显不同,VDR基因多态性与围绝经期妇女骨密度有部分相关性,ER基因与骨密度无明显关系。     

武汉地区汉族人群ALDH2基因多态性的分布研究

目的研究湖北武汉地区汉族人群中的乙醛脱氢酶2(ALDH2)*2等位基因及基因型的频率分布特征。方法利用基因芯片杂交技术检测样本基因型,对465名(262名男性,203名女性)湖北武汉地区汉族人群进行ALDH2*2基因多态性分析,将结果与文献报道的其他地区及不同民族进行比较,并比较本地区不同性别间基因多态性的差异。结果 465名武汉地区汉族人群中ALDH2*1和*2等位基因频率分别为80.22%和19.78%;湖北武汉地区汉族人群ALDH2基因型与洛阳、青岛、上海等城市地区的人群间差异无统计学意义(P> 0.05);不同民族间ALDH2等位基因和基因型各不相同,武汉地区汉族人群与壮族、维族、朝鲜族和鄂伦春族地区人群的差异具有统计学意义(P <0.05),与藏族、回族、蒙族和白族地区人群的差异无统计学意义(P> 0.05);不同国家之间比较,中国人群ALDH2等位基因及基因型频率与日本、印度、土耳其和美国人群的差异具有统计学意义(P <0.05);不同性别比较,男性与女性ALDH2等位基因与基因表型间差异无统计学意义(P> 0.05)。结论 ALDH2*2基因多态性分布在不同民族和国家之间差异具有统计学意义,而在不同地区和不同性别之间差异不具有统计学意义。     

中国汉族人群hGSTA1基因C-69T多态性分析

目的　研究中国汉族人群中人谷胱甘肽S 转移酶(hGSTA1 )C-69T基因多态性的分布。方法1 4 0例血样本来自中国2 5个省份的汉族人口,用聚合酶链反应 限制性片段长度多态性方法检测hGSTA1 69位点的变异。结果　中国汉族人群GSTA1基因 69位点的野生型纯合子(CC)基因型的分布频率为75 .0 %,突变型纯合子(TT)基因型为0 .7%,杂合子(CT)基因型为2 4 .3 %;C及T两种等位基因的频率分别为87.1 %及1 2 .9%。结论中国汉族人群GSTA1基因呈多态性分布,其等位基因和基因型频率不同于其他种族     

贵州汉族人群支气管哮喘患者β2-肾上腺素能受体基因多态性的研究

目的探讨贵州汉族人群β2-肾上腺素能受体(β2-AR)16、27位点基因多态性与支气管哮喘的相关性.方法采用等位基因特异性聚合酶链反应(AS-PCR)方法,对74例支气管哮喘患者、39例健康者进行β2-AR基因多态性分析.结果 (1)贵州汉族人群β2-AR基因16、27位点多态性分布频率与英美高加索人群不同,与国内有关报道结果一致;(2)支气管哮喘组人群β2-AR基因16位点多态性分布频率杂合子基因型占47.2%,甘氨酸纯合子基因型占35.2%,与健康组比较,差异有显著意义(P＜0.05),而等位基因频率与健康组比较,差异无显著意义(P＞0.05);27位点多态性分布频率谷氨酰胺纯合子基因型占52.7%,杂合子基因型占33.7%,谷氨酸纯合子基因型占13.6%,以及等位基因频率与健康组比较,差异无显著意义(P＞0.05).结论贵州汉族人群中β2AR基因16位点多态性与支气管哮喘相关联;27位点多态性与支气管哮喘无关联.     

遵义地区人群维生素D受体基因外显子2多态性

目的探讨遵义地区人群维生素D受体（VDR）基因第2外显子（起始密码子,e2）的单核苷酸多态性分布情况。方法收集110例遵义地区汉族人群静脉血标本,采用聚合酶链反应．限制性片段长度多态性法测定VDR基因e2序列多态性．分析该人群中基因型频率和基因频率分布规律。结果FokI的等位基因频率为F0．741、f0．259。结论VDR基因e2序列在遵义地区汉族中的分布具有多态性。     

VDR基因启动子单核苷酸多态性与前列腺癌的关系

目的了解维生素D受体（vitamin D receptor,VDR）基因启动子上存在的单核苷酸多态性（single nucleotide polymorphism,SNP）与前列腺癌的关系,进而探讨导致前列腺发病的遗传因素。方法提取60例前列腺癌及50例良性前列腺增生患者外周血标本中基因组DNA,应用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction—restriction fragment length polyinorphisin,PCR—RFLP）检测并分析了VDR基因起始密码SNP在两组中的分布。常规病理方法分析前列腺癌的Gleason评分。对比分析VDR基因上存在的SNP与前列腺癌发生发展的相关性。结果前列腺癌组和前列腺增生组Fok Ⅰ等位基因多态性分布筹异有统计学意义（P〈0．05）,高危组和低危组前列腺癌中VDR基因SNP分布的的差异有统计学意义（P〈0．05）。结论VDR基因起始密码SNP不同类型可能与前列腺癌的发生有相关性。不同SNP类型可能成为前列腺癌发展的危险因素。     

Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk

The association between vitamin D receptor (VDR) gene polymorphisms and diseases such as breast cancer, prostate cancer and osteoporosis has been extensively investigated during recent years. To date, several polymorphisms have been found in the VDR gene. In this Finnish case-control study, comprising 483 breast cancer patients and 482 healthy population controls, we investigated the association between altered breast cancer risk and two polymorphisms in the 3' end of the gene detectable with ApaI and TaqI restriction enzymes. A statistically significant difference was observed in the ApaI genotype distribution between cases and controls. Women with the VDR variant a allele containing genotypes showed a decreased risk for breast cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.54-0.98] compared to women with the AA genotype. This association was especially strong among women with a positive family history of breast cancer (OR 0.14, 95% CI 0.03-0.76). Moreover, there was a trend (P for trend = 0.0007) for decreased risk with increasing number of variant alleles. The lowest risk of breast cancer was seen for the women with the aa genotype (OR 0.03, 95% CI 0.003-0.31) compared to women with the AA genotype. A tendency of decreased risk of breast cancer was also observed for the TaqI T allele containing genotypes (Tt and TT) (OR 0.68, 95% CI 0.41-1.12), but because the distribution of Taql alleles in the controls missed the Hardy-Weinberg equilibrium (P = 0.01), we were unable to properly assess the potential impact of the TaqI polymorphism in breast cancer susceptibility. In conclusion, our results suggest that the VDR ApaI genotype may be an important modifier of individual breast cancer risk among Finnish women, especially if they have a positive family history of breast cancer.     

维生素D受体基因Fok I多态性与1型糖尿病的相关性研究

目的探讨维生素D受体（VDR）基因FokI位点多态性与1型糖尿病（T1DM）的关系。方法研究纳入T1DM患者241例和正常对照组380例。VDR基因FokI位点基因型采用聚合酶链反应-限制性片断长度多态（PCR-RFLP）法检测。结果 T1DM组VDR基因FokI基因型分布和F/f等位基因频率与对照组比较,两者间的差异无统计学意义（P〉0.05）。在T1DM组中,Ff基因型组与ff基因型组的空腹-C肽（FCP）和餐后C-肽（PCP）均低于FF基因型组,差异具有统计学意义（P〈0.05）。结论 VDR基因FokI多态性与T1DM遗传易感性不相关。T1DM患者中ff基因型与Ff基因型组FCP和PCP呈低水平,提示VDR基因FokI基因型可能与胰岛细胞功能相关。     

Polymorphisms of vitamin D receptor gene protect against the risk of head and neck cancer

Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described, including a FokI restriction fragment-length polymorphism (RFLP) in exon 2 and an adjacent TaqI RFLP in exon 9. We hypothesized that the VDR FokI and TaqI polymorphisms are associated with the risk of developing squamous cell carcinoma of the head and neck (SCCHN). We conducted a hospital-based, case-control study of 719 SCCHN cases and 821 cancer-free controls (all non-Hispanic Whites) to assess the association between VDR polymorphisms and SCCHN risk. The cases and controls were frequency-matched on age, sex and ethnicity. Polymorphisms at the TaqI and FokI restriction sites were determined from genomic DNA by polymerase chain reaction-RFLP methods. Both homozygous variant genotypes (ff and tt) were associated with a decreased risk of SCCHN [odds ratio (OR)=0.72, 95% confidence interval (CI)=0.53-0.98 and OR=0.64, 95% CI=0.47-0.87, respectively] compared to the common FF and TT genotypes. The VDR variant genotypes were associated with a decreasing risk of SCCHN in a variant allele dose-dependent manner, and the decreasing trend in OR was statistically significant, particularly for the combined genotypes (Ptrend<0.001). These data suggest that the VDR f and t alleles and their genotypes may protect against SCCHN. However, further studies are warranted to confirm these findings.     

Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe

Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nucleotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted.     

Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects

Genetic factors influence whole blood lead (Pb-B) concentrations in lead exposed subjects. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms (BsmI, ApaI and FokI) in vitamin D receptor (VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects. Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb (BsmI polymorphism) or ff (FokI polymorphism) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa (ApaI polymorphism) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI, BsmI, and FokI polymorphisms, respectively, compared with the other haplotype groups, thus suggesting that VDR haplotypes modulate the circulating levels of lead in exposed subjects.     

AT1R基因多态性与肺原性心脏病的相关性

目的通过对肺心病患者AT1R基因多态性的检测,从分子水平探讨肺原性心脏病(肺心病)的发病机理,寻找肺心病发病的相关致病基因。方法应用多聚酶链反应(PCR)技术,检测40名正常人和60例肺心病患者AT1R、ACE的基因型和等位基因频率。结果①正常对照组AT1R基因型分布为AA型85.0%,AC型15.0%;肺心病组AT1R基因型分布为AA型70.3%,AC型29.7%;统计学分析两组间基因型构成、A和C等位基因频率均无显著性差异;②女性肺心病患者AT1R基因型分布AA型70.4%,AC型29.6%,无CC型,等位基因频率A型为85.2%,C型为14.8%;男性肺心病患者AT1R基因型分布为AA型69.7%,AC型30.3%,无CC型,等位基因频率A型为84.8%,C型为15.2%;统计学分析两组间基因型构成、等位基因频率无显著性差异;③在肺心病伴有肺栓塞组的19例患者AT1R基因AA型、AC型和CC型分别为84.2%、15.8%和0,等位基因频率A型为92.1%,C型为7.9%;统计学分析肺心病伴肺栓塞组与正常对照组基因型构成、等位基因频率比较无显著性差异。结论①AT1R A1166C多态性与肺心病发生以及肺心病伴肺栓塞无明显相关性;②肺心病组和AA基因型患者组与正常对照组平均红细胞压积无明显相关性。     

Interaction effects between estrogen receptor α and vitamin D receptor genes on age at menarche in Chinese women

AIM: To evaluate whether estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes are associated with the age at menarche in Chinese women. METHODS: A total of 390 pre-menopausal Chinese women were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: Neither the ER-alpha gene nor the VDR gene individually had significant effects on the age at menarche in our subjects (P>0.10). However, evidence of interaction effects between the two genes were observed: with the aa genotype at the VDR ApaI locus, subjects with haplotype PX at the ER-alpha gene had, on average, 6 months later onset of menarche than the non-carriers (P=0.01). CONCLUSION: We found that neither the ER-alpha gene or the VDR gene had a significant association with the age at menarche individually. However, potential interaction effects between the two genes were observed in Chinese women.     

Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women

AIM: To investigate the possible association of Q89R, N740N and A1330V polymorphisms in low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD) in postmenopausal Chinese women. METHODS: Q89R, N740N and A1330V genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 647 unrelated healthy postmenopausal Han Chinese women aged 43-76 years in Shanghai. BMD at lumbar spine 1-4 and the left proximal femur including the femoral neck, trochanter and Ward's triangle were measured by dual-energy X-ray absorptionmetry in all subjects. RESULTS: The distribution of the Q89R, N740N and A1330V genotypes in this population was as follows: QQ 80.5%, QR 18.7%, and RR 0.8%; TT 66.9%, TC 31.1%, and CC 2.0%; AA 68.0%, AV 29.7%, and VV 2.3%. The frequencies of the Q89R, N740N and A1330V genotypes and alleles did not deviate from the Hardy-Weinberg equilibrium. We found that the Q89R and A1330V polymorphisms were in linkage disequilibrium in our population (kappa2=13.50, P<0.01). Both before and after adjusting for age, years since menopause, height, and weight, the Q89R or N740N genotypes were significantly associated with BMD at the femoral neck (P<0.05). Subjects with the Q89R QQ genotype or the N740N TT genotype had a significantly higher BMD at the femoral neck, compared with those with the QR/RR or TC/CC genotypes, respectively. No significant association was found between A1330V polymorphism and BMD at any site. CONCLUSION: Our findings suggest that the LRP5 gene is a candidate for the genetic determination of BMD in postmenopausal Chinese women.