卵泡刺激素受体基因多态性的研究进展

卵泡刺激素是人类重要的生殖激素,通过其受体介导生理功能.目前在卵泡刺激素受体基因中发现大量单核苷酸多态性,特别是Asn 680Ser,可能影响受体活性,引起卵巢功能差异,并与辅助生殖技术中的卵巢刺激反应有一定联系.为即将进行卵巢刺激的患者测定基因多态性,以此定做个体化的卵巢刺激方案具有临床意义.其可以优化不孕症的治疗,减少医源性疾病的产生.但仍需要更多的临床实验检验其有效性.     

卵泡刺激素受体基因多态性的研究进展

卵泡刺激素是人类重要的生殖激素,通过其受体介导生理功能。目前在卵泡刺激素受体基因中发现大量单核苷酸多态性,特别是Asn680Ser,可能影响受体活性,引起卵巢功能差异,并与辅助生殖技术中的卵巢刺激反应有一定联系。为即将进行卵巢刺激的患者测定基因多态性,以此定做个体化的卵巢刺激方案具有临床意义。其可以优化不孕症的治疗,减少医源性疾病的产生。但仍需要更多的临床实验检验其有效性。     

卵泡刺激素受体基因与卵巢功能的研究进展

卵泡刺激素（FSH）在人类生殖过程中发挥着重要作用,其对卵巢的作用主要是通过与卵巢颗粒细胞膜表面的特异性受体即卵泡刺激素受体（FSHR）结合来发挥的。FSHR基因结构的正常与否直接影响着卵巢的生殖和内分泌功能,FSHR启动子激活后能启动FSHR基因转录,并进一步引起FSHR基因转录后水平的变化,从而引起卵巢功能的改变。FSHR基因点突变既可以导致卵巢功能活化（如反复自发性卵巢过度刺激综合征）,又可以引起卵巢功能失活（如女性卵巢早衰）。对FSHR基因的正常结构与卵巢功能的关系及FSHR基因点突变与卵巢功能改变的关系综述如下。     

卵泡刺激素基因多态性与不孕妇女卵巢反应相关性研究

目的 探讨卵泡刺激素受体(FSHR)基因680位点单核苷酸多态性对体外受精-胚胎移植(IVF-ET)患者卵巢反应性和妊娠结局的影响。方法 选取通过IVF-ET助孕的患者120例,其中卵巢低反应和高反应患者各30例,卵巢反应正常患者60例,通过直接测序来检测FSHR基因680外显子的多态性,根据检测结果分为NN组、NS组及SS组,对3组间卵巢反应和移植后临床结局进行比较。结果 SS纯合型患者基础FSH水平显著高于NN和NS型(P<0.05),NN型患者获卵数显著高于SS型(P<0.05),3组患者间临床妊娠率比较,差异无统计学意义(P>0.05)。结论 680位点SS基因型可能会引起患者卵巢在促排卵过程中反应性过低,本研究未发现该位点多态性对临床妊娠率的影响。     

卵泡刺激素受体基因与卵巢功能的研究进展

卵泡刺激素(FSH)在人类生殖过程中发挥着重要作用,其对卵巢的作用主要是通过与卵巢颗粒细胞膜表面的特异性受体即卵泡刺激素受体(FSHR)结合来发挥的.FSHR基因结构的正常与否直接影响着卵巢的生殖和内分泌功能,FSHR启动子激活后能启动FSHR基因转录,并进一步引起FSHR基因转录后水平的变化,从而引起卵巢功能的改变.FSHR基因点突变既可以导致卵巢功能活化(如反复自发性卵巢过度刺激综合征),又可以引起卵巢功能失活(如女性卵巢早衰).对FSHR基因的正常结构与卵巢功能的关系及FSHR基因点突变与卵巢功能改变的关系综述如下.     

卵泡刺激素受体基因多态性与多囊卵巢综合征关系的研究进展

多囊卵巢综合征(PCOS)是一种高度异质性生殖内分泌紊乱性疾病,对女性生活产生极大影响。卵泡刺激素(FSH)通过与分布在性腺上的特异性卵泡刺激素受体(FSHR)结合,起到促进和维持正常的性腺发育和生殖功能,FSHR是PCOS易感基因的位点之一。近年来,FSHR基因多态性相关研究较多,FSHR基因突变可降低FSH敏感性,雄激素水平升高,导致排卵功能障碍,影响辅助生殖等。本文对FSHR基因多态性及其对PCOS的影响进行综述,为PCOS发病风险的评估及其遗传学相关研究提供一定的理论依据。     

Toll样受体单核苷酸多态性与疾病易感性的关系

基因多态性与机体对疾病的遗传易感性相关。Toll样受体(TLRs)在识别病原微生物、启动炎性应答中起重要作用。越来越多数据表明,TLRs单核苷酸多态性(SNPs)与炎性应答损伤及感染性疾病的遗传易感性相关,如TLR4基因Asp299Gly和Thr399Ile SNPs与多种感染性疾病正相关,而在动脉粥样硬化及其相关疾病中则起保护作用[1]。笔者就TLRs SNPs与感染性疾病的遗传易感性进行综述。1 Toll样受体与免疫应答近来认为,机体针对病原微生物等病原相关分子模式的入侵所产生的先天及特异性免疫由模式识别受体(PRRs)启动。TLRs是主要的PRRs,能调节…     

雌激素受体β基因多态性与子宫肌瘤相关性研究

目的:探讨雌激素受体β基因多态性与中国北方汉族人群子宫肌瘤的关系。方法:采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法检测167例子宫肌瘤患者和170例健康女性的雌激素受体β基因rs1256064和rs1256049SNPs位点的基因型,应用SPSS12.0分析基因多态性与子宫肌瘤的相关性。结果:病例组与对照组人群2个SNPs的基因型分布均符合Hardy-W e inberg平衡定律;rs1256064位点的等位基因及基因型的频数在病例组和对照组间的分布差异有统计学意义(P<0.05),rs1256049位点的基因型频数在病例组和对照组间的分布差异无统计学意义,而等位基因的频数分布差异有统计学意义(P<0.05)。结论:雌激素受体β基因rs1256064位点基因多态性可能与中国北方汉族人群子宫肌瘤相关联。     

雌激素受体单核苷酸多态性与子宫颈癌的相关性研究

目的 探讨雌激素受体(GPR30)单核苷酸多态性与子宫颈癌的相关性.方法 选取114例子宫颈癌患者为研究组,同数量子宫息肉及子宫肌瘤等良性疾病者为对照组,采用S-P免疫组化法测定子宫颈癌组织GPR30表达,PCR-RFLP法测定GPR30(rs3808351)位点基因多态性.结果 对照组与研究组在怀孕次数、首次性生活年龄、文化程度及HPV感染方面有统计学差异(χ2=20.64、14.05、10.11、39.71,P<0.05);研究组GPR30阳性表达率显著高于对照组(χ2=12.65,P<0.05);对照组与研究组GG、AA基因型比较差异有统计学意义(χ2值分别为6.14、5.89,均P<0.05),G、A等位基因频率比较差异有统计学意义(χ2值分别为5.63和5.76,均P<0.05);Logistic回归分析显示,怀孕次数(OR=1.659,95%CI:1.231~4.964,P<0.05)、HPV感染(OR=1.778,95%CI:1.196~3.854,P<0.05)、G等位基因频率(OR=2.239,95%CI:1.545~7.032,P<0.05)为子宫颈癌的危险因素.结论 GPR30(rs2808350)位点G等位基因频率可能为子宫颈癌的发生危险因素.     

β2肾上腺素受体基因单核苷酸多态性与河南汉族原发性高血压关系的研究

[目的]探讨β2肾上腺素受体(β2-adrenergic receptor,β2-AR)基因+46(G→A)位和+79(G→C)位单核苷酸多态性(single nucleotide polymorphisms,SNP)与河南汉族原发性高血压(essential hypertension,EH)的相关性.[方法]应用PCR-RFLP的方法,检测汉族高血压患者96例和正常血压者196例的β2-AR基因+46和+79位单核苷酸多态性,并运用卡方分析数据.[结果]两种SNPs基因型分布符合Hardy-Weinberg平衡,+46(G→A)的基因型分布在高血压和对照组的差异无统计学意义(P>0.05),+79(G→C)的基因型分布在高血压和对照组中全部是GG,不存在基因多态性.从而得知我国河南汉族人群中β2-AR基因46位点和79位点多态性与高血压病无相关性.但46位点在女性人群中差异有统计学意义(P<0.05),与高血压病相关.[结论]46位点可能是河南汉族女性群体原发性高血压遗传的易感性标志之一.     

Single nucleotide polymorphisms of USP26 in azoospermic men

Some studies have focused on the association between male infertility and single nucleotide polymorphisms (SNPs) in the ubiquitin-specific protease 26 (USP26) gene, but the results are controversial. In this case-control study including both normozoospermic men and patients with nonobstructive azoospermia, we analyzed both the entire coding region and 5’ and 3’ untranslated regions of USP26 in order to identify genetic variants in this gene to investigate the role of USP26 on spermatogenesis. We reported variations in the USP26 gene sequence in 82% of azoospermic and in 50% normospermic men. The synonymous variation c.576G>A has a frequency significantly different in the azoospermic (60.2%) and normozoospermic (23.6%) groups, while the frequencies in the two groups of both c.1090C>T and c.1737G>A missense mutations did not reach statistical significance. A cluster mutation (c.371insACA, c.494T>C) was detected in 2 normozoospermic men (2.7%). In the 5’UTR we identified the -33C>T variation both in azoospermic (3.8%) and in normozoospermic (2.7%) men. In a normozoospermic man we detected the nonsense mutation c.882C>A, never reported to date. According to our results, we suggest that only the variation c.576G>A has a frequency significantly different in azoospermic compared to normozoospermic men. Moreover, the identification in a normozoospermic man of a nonsense mutation (c.882C>A) which causes the production of a truncated protein, suggests a marginal role of USP26 in male spermatogenesis. Additional studies may be useful as we cannot exclude that the other SNPs may represent risk factors for male fertility acting by an oligogenic/polygenic mechanism.     

Single nucleotide polymorphisms in Plasmodium falciparum V type H+ pyrophosphatase gene (pfvp2) and their associations with pfcrt and pfmdr1 polymorphisms

BackgroundChloroquine resistance in Plasmodium falciparum malaria has been associated with pfcrt 76T (chloroquine resistance transporter gene) and pfmdr1 86Y (multidrug resistance gene 1) alleles. Pfcrt 76T enables transport of protonated chloroquine out of the parasites digestive vacuole resulting in a loss of hydrogen ions (H⁺). V type H⁺ pyrophosphatase (PfVP2) is thought to pump H⁺ into the digestive vacuole. This study aimed to describe the geographic distribution of single nucleotide polymorphisms in pfvp2 and their possible associations with pfcrt and pfmdr1 polymorphisms.MethodsBlood samples from 384 patients collected (1981–2009) in Honduras (n = 35), Colombia (n = 50), Liberia (n = 50), Guinea Bissau (n = 50), Tanzania (n = 50), Iran (n = 50), Thailand (n = 49) and Vanuatu (n = 50) were analysed. The pfcrt 72–76 haplotype, pfmdr1 copy numbers, pfmdr1 N86Y and pfvp2 V405I, K582R and P711S alleles were identified using PCR based methods.ResultsPfvp2 was amplified in 344 samples. The pfvp2 allele proportions were V405 (97%), 405I (3%), K582 (99%), 582R (1%), P711 (97%) and 711S (3%). The number of patients with any of pfvp2 405I, 582R and/or 711S were as follows: Honduras (2/30), Colombia (0/46), Liberia (7/48), Guinea-Bissau (4/50), Tanzania (3/48), Iran (3/50), Thailand (1/49) and Vanuatu (0/31). The alleles were most common in Liberia (P = 0.01) and Liberia + Guinea-Bissau (P = 0.01). The VKP haplotype was found in 189/194 (97%) and 131/145 (90%) samples harbouring pfcrt 76T and pfcrt K76 respectively (P = 0.007).ConclusionsThe VKP haplotype was dominant. Most pfvp2 405I, 582R and 711S SNPs were seen where CQ resistance was not highly prevalent at the time of blood sampling possibly due to greater genetic variation prior to the bottle neck event of spreading CQ resistance. The association between the pfvp2 VKP haplotype and pfcrt 76T, which may indicate that pfvp2 is involved in CQ resistance, should therefore be interpreted with caution.     

Bioinformatics of varicella-zoster virus: Single nucleotide polymorphisms define clades and attenuated vaccine genotypes

Varicella zoster virus (VZV) is one of the human herpesviruses. To date, over 40 complete VZV genomes have been sequenced and analyzed. The VZV genome contains around 125,000 base pairs including 70 open reading frames (ORFs). Enumeration of single nucleotide polymorphisms (SNPs) has determined that the following ORFs are the most variable (in descending order): 62, 22, 29, 28, 37, 21, 54, 31, 1 and 55. ORF 62 is the major immediate early regulatory VZV gene. Further SNP analysis across the entire genome has led to the observation that VZV strains can be broadly grouped into clades within a phylogenetic tree. VZV strains collected in Singapore provided important sequence data for construction of the phylogenetic tree. Currently five VZV clades are recognized; they have been designated clades 1 through 5. Clades 1 and 3 include European/North American strains; clade 2 includes Asian strains, especially from Japan; and clade 5 includes strains from India. Clade 4 includes some strains from Europe, but its geographic origins need further documentation. Within clade 1, five variant viruses have been isolated with a missense mutation in the gE (ORF 68) glycoprotein; these strains have an altered increased cell spread phenotype. Bioinformatics analyses of the attenuated vaccine strains have also been performed, with a subsequent discovery of a stop-codon SNP in ORFO as a likely attenuation determinant. Taken together, these VZV bioinformatics analyses have provided enormous insights into VZV phylogenetics as well as VZV SNPs associated with attenuation.     

Single nucleotide polymorphisms in cell wall biosynthesis-associated genes and phylogeny of Mycobacterium tuberculosis lineages

To investigate specific single nucleotide polymorphisms (SNPs) of different lineages of Mycobacterium tuberculosis, cell wall biosynthesis-associated genes encoding antigen 85 complex (fbpA, fbpB, and fbpC) and mannosyltransferase (pimB) were analyzed. Genetically diversified and predominant M. tuberculosis and Mycobacterium bovis genotypes identified in Taiwan (26 Beijing and 44 non-Beijing) were included in the study. Sequence analyses revealed that nine novel SNPs were found within main lineages of M. tuberculosis complex, including East-African-Indian (EAI), Beijing, Central-Asian (CAS), Bovis, and one lineage containing Latin American and Mediterranean (LAM), Haarlem and T. Specifically, a SNP in pimB codon 270 was identified in EAI, fbpA codon 156 in ancestral Beijing, fbpB codon 238 in modern Beijing, fbpA codon 4 and fbpC codon 158 in CAS, fbpA codon 311 in M. bovis and an additional SNP in fbpB codon 140 in M. bovis-BCG, and pimB codon 107 in other spoligotypes lineages including an additional SNP in fbpC codon 103 in LAM. In addition, we proved that isolates with spoligotype shared type (ST) no. 523 (carrying all 43 spacers), designated as unknown lineage in an international spoligotyping database (SpolDB4), belong to an early ancestral Beijing sublineage. Accordingly, a phylogenetic tree was constructed using those SNPs, and an evolutionary hypothesis for lineages of M. tuberculosis was proposed. These novel lineage-specific SNPs will be informative genetic markers in molecular epidemiological and evolutionary studies of M. tuberculosis.     

Single nucleotide polymorphisms in sweet,fat, umami,salt, bitter and sour taste receptor genes are associated with gustatory function and taste preferences in young adults

Taste is a fundamental mechanism whereby compounds are detected orally, yet it is highly variable among individuals. The variability in taste that is attributable to genetics is not well-characterized despite its potential role in food selection, and therefore, eating habits that contribute to risk of overweight and obesity. In order to implicate measures of taste function and preference as potentially deterministic factors in adverse eating behaviors that lead to obesity, it must be shown that a relationship exists between genetic variation in taste receptor genes and psychophysical measures of taste in the absence high body mass index. The primary objective of this pilot study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in taste receptor genes and 3 different psychophysical measures of taste in healthy young adults. Sweet, salt, umami, fat, sour, and bitter taste receptor gene SNPs were genotyped in 49 participants (ages 24.6 ± 0.6 years) who completed testing to determine oral detection threshold (DT), suprathreshold sensitivity (ST) and taste preference (PR). A simultaneous association test was conducted between each SNP and the 3 taste outcomes (DT, ST, and PR). Twelve SNPs were associated with at least one of the 3 taste outcomes. Associations were observed between SNPs in taste receptor genes and psychophysical measures of sweet, fat, umami, and salt taste. These results suggest that differences in interindividual psychophysical measures of tastes, namely DT, ST, and PR, may be partially attributed to genetic variation in taste receptor genes. Future studies are warranted to investigate if these findings have consequences for habitual dietary intake of foods that elicit these tastes.     

Single nucleotide polymorphisms of ADRB2 gene and their association with susceptibility for Plasmodium falciparum malaria and asthma in an Indian population

The essential route to blood parasitaemia in malaria, erythrocyte invasion is facilitated by activation of the G-protein coupled receptor signaling pathway mediated by the β2-adrenoreceptor as one of the proteins on the surface of red blood cells. The effectiveness of bronchodilators and inhaled corticosteroids in the clinical treatment for asthma patients also depend on polymorphisms in the β2-adrenoreceptor gene (ADRB2). In a case control study, individuals affected by Plasmodium falciparum malaria, asthma and controls were tested for association of six ADRB2 single nucleotide polymorphisms (SNPs) viz. rs1042711, rs1801704, rs1042713, rs1042714, rs1042717 and rs1042718, by direct DNA sequencing. The rs1801704 locus was significantly associated with malaria when compared against controls. The rs1042713 polymorphism was associated with forced expiratory flow between 25% and 75% of the FVC in asthma patients, pre (p = 0.048) and post (p = 0.038) treatment measurements. Predicted haplotype of the six SNPs computed from genotype data showed T-T-A-C-G-C conferred significant risk of malaria (p = 0.02) whereas T-T-A-C-G-A was associated with risk of asthma (p = 0.02). The haplotype T-T-G-C-G-C was protective against both malaria (p = 0.02) as well as asthma (p = 0.026) and C-C-G-G-G-C was protective uniquely for asthma (p = 0.04). A significant outcome was that all variant alleles at the SNP loci were part of the haplotype conferring resistance to malaria disease and asthma, except rs1042713 and rs1042718 which showed very high frequency in asthma. The pairwise linkage disequilibrium (LD) estimates showed a distinct LD block of all SNP loci (D′ = 1 or >0.8) in malaria patients. This characteristic haplotype block was disrupted in the controls due to non-significant pairwise LD of the SNP loci; and a more extensive disruption of the block was noted in asthma patients. The study provides evidence for the proposed role of β2-adrenoreceptor mediated molecular mechanisms in etiology of malaria, as well as asthma disease and drug response, for further clinical and therapeutic application studies.     

瘦素受体基因多态性与壮族儿童单纯性肥胖的相关性研究

目的 探讨瘦素受体(leptin receptor,LEPR)基因单核苷酸多态性位点rs1137100 与壮族儿童单纯性肥胖的相关性。方法 对208名柳州某区小学学龄前儿童(年龄均<7岁)分别检测身高和体重,计算BMI。利用SNaPshot技术分析107例单纯性肥胖儿童和101例健康对照儿童的LEPR 基因型及等位基因频率分布状况。结果 肥胖和健康对照组LEPR 基因A/A型、A/G型及G/G型基因型频率分别为66.4%、29.9%、3.7%和68.3%、27.7%、4.0%,两组等位基因频率分别为81.3%、18.7%和82.2%、17.8%,A等位基因的OR值为1.06,95%CI为0.64~1.74。两组基因型与等位基因频率差异均无统计学意义(P>0.05);肥胖与健康对照组LEPR 基因型频率在性别分层中差异均无统计学意义(P>0.05)。肥胖组的BMI水平明显高于对照组,差异有统计学意义(P<0.05)。而肥胖组中各基因型间BMI水平的差异无统计学意义(P>0.05)。经Hardy-Weinberg遗传平衡定律检验,其等位基因在两种人群中的分布符合遗传平衡,说明样本具有群体代表性。而该位点的等位基因及基因型频率在所收集的肥胖组与对照组样本中分布未见显著异常。结论 LEPR基因rs1137100位点多态性与广西壮族学龄前儿童单纯性肥胖无相关性。     

汉坦病毒感染者与非感染者HLA-B、DQ基因单核苷酸多态性研究

目的 分析肾综合征出血热（HFRS）患者和健康人群HLA-B及HLA-DQ基因区域的单核苷酸多态性（SNP）位点,探讨人感染汉坦病毒与其遗传特性间的关联性。方法 采用等位基因特异性引物扩增（ASP-PCR）技术对HLA-B及HLA-DQ区域上的5个SNP位点进行扩增,利用病例对照研究探讨SNP与人群汉坦病毒感染状态之间的关系。结果 筛选HFRS患者阳性标本24份,同时采集与病例相匹配的健康人群标本51份。rs34933313位点患者组和对照组的CC基因型频率分别为4.17%和29.41%,GG基因型为12.50%和15.69%,CG基因型为83.33%和54.90%,CC、GG基因型频率患者组低于对照组,CG基因型频率患者组高于对照组,且二者之间差异有统计学意义（χ2=7.050,P=0.029）。其他4个位点两组间的差异均无统计学意义。结论 rs34933313位点的基因多态性可能与人群汉坦病毒感染有关,可能会增加人群感染该病毒的风险。HLA-B基因可能与人群感染汉坦病毒存在相关性。