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Study of the potential association of the BCHE rs1803274 genetic polymorphism and serum level of its protein with breast cancer BCHE rs1803274基因多态性及其血清蛋白水平与乳腺癌的潜在关联研究
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100913
Mona S. Habieb , Nesreen G. Elhelbawy , Alshimaa M. Alhanafy , Mohammad G. Elhelbawy , Ahmed S. Alkelany , Amany M. Wahb

Background

Genetic-based individual differences remain a promising area for studying cancer susceptibility. BCHE gene encodes the butyrylcholinesterase (BChE) enzyme, which has been linked to inflammation and tumor genesis. The commonest missense mutation of BCHE gene is the rs1803274 G/A polymorphism. We aimed to analyze BCHE rs1803274 gene polymorphism in terms of distribution among breast cancer patients, its effect on enzyme activity and its correlation with clinic pathological parameters.

Methods

160 breast cancer female patients matched by age with 120 female healthy controls were recruited. CA 15–3 and CEA were measured by ELISA. BChE activity was measured by spectrophotometry. BCHE rs1803274 polymorphism was analyzed by real time- PCR.

Results

Significant higher prevalence of GA genotype and A allele were observed in patients [P < 0.001, OR (95% CI); 3.12 (1.67–5.85), P < 0.001, OR (95% CI); 2.86 (1.68–4.87) respectively]. This significance was observed under the dominant mode of inheritance (P < 0.001, OR (95% CI); 3.22 (1.78–5.85). GA + AA patients showed significant association with tumor grade, stage, and metastasis (P < 0.001). GA + AA patients exhibited significantly lower BChE activity compared to GG patients (3648.5 (2968–4332) mU/ml and 7128.5 (6332–8341) mU/ml respectively, P < 0.001).

Conclusions

Higher frequency of the A-variant of BCHE rs1803274 and the associated low activity of BChE in breast cancer patients could represent susceptibility elements for development of breast cancer. Moreover, the rs1803274 is linked to some tumor features, which could be a proof of its prognostic value.

基于遗传的个体差异仍然是研究癌症易感性的一个有前途的领域。BCHE基因编码与炎症和肿瘤发生有关的丁基胆碱酯酶(BCHE)。BCHE基因最常见的错义突变是rs1803274 G/A多态性。我们旨在分析BCHE rs1803274基因多态性在乳腺癌患者中的分布、对酶活性的影响及其与临床病理参数的相关性。方法选取160例年龄匹配的女性乳腺癌患者和120例健康对照。ELISA法检测ca15 - 3和CEA。用分光光度法测定BChE活性。实时荧光定量PCR检测BCHE rs1803274基因多态性。结果GA基因型和A等位基因在患者中的患病率明显高于对照组[P <0.001,或(95% ci);3.12 (1.67-5.85), P <0.001,或(95% ci);分别为2.86(1.68-4.87)。这种显著性在显性遗传模式下被观察到(P <0.001,或(95% ci);3.22(1.78 - -5.85)。GA + AA患者与肿瘤分级、分期和转移有显著相关性(P <0.001)。GA + AA患者BChE活性明显低于GG患者(分别为3648.5 (2968-4332)mU/ml和7128.5 (6332-8341)mU/ml);0.001)。结论乳腺癌患者BCHE rs1803274 a型变异频率较高,BCHE活性较低,可能是乳腺癌发生的易感因素。此外,rs1803274与一些肿瘤特征有关,这可能是其预后价值的证明。
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引用次数: 2
Atypical phenotype in a patient with ceruloplasmin mutations in the compound heterozygous state 复合杂合状态下铜蓝蛋白突变患者的非典型表型
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100905
Giulia Ravasi , Sara Pelucchi , Francesco Canonico , Raffaella Mariani , Alberto Piperno

Aceruloplasminemia is an ultra-rare and fatal autosomal recessive disease with a long lasting neurological disabling period of life caused by mutations in ceruloplasmin gene. Disease phenotype is heterogeneous and variably characterized by iron-restricted erythropoiesis and microcytic anemia, hyperferritinemia with tissue iron accumulation in liver, pancreas and brain, diabetes, retinopathy and neurodegeneration. Although most heterozygotes are asymptomatic, they might present with significant neurological symptoms at some point in their lives. We report here a patient with hyperferritinemia and severe depressive disorder, harbouring two mutations in ceruloplasmin in the compound heterozygous state (p.Pro477Leu and p.Gly895Ala). Both mutations are classified as deleterious in silico, but in vitro functional study partially confirmed it. Our findings suggest that the two mutations cooperate in inducing low ceruloplasmin production in the range observed in aceruloplasminemia heterozygotes and raise the question whether this might increase patient's susceptibility to neurologic manifestations.

铜蓝蛋白血症是一种由铜蓝蛋白基因突变引起的超罕见、致死性常染色体隐性遗传病,具有长期的神经系统失能期。疾病表型是异质性和可变的,以铁限制性红细胞和小细胞性贫血为特征,高铁蛋白血症伴肝、胰腺和脑组织铁积累,糖尿病,视网膜病变和神经变性。虽然大多数杂合子是无症状的,但他们可能在生命的某个阶段出现明显的神经系统症状。我们在此报告一位患有高铁蛋白血症和严重抑郁症的患者,在复合杂合状态下携带两个铜蓝蛋白突变(p.Pro477Leu和p.Gly895Ala)。这两种突变在计算机上都被归类为有害的,但在体外功能研究中部分证实了这一点。我们的研究结果表明,这两种突变共同诱导了在紫纤溶酶血症杂合子中观察到的范围内的低铜蓝蛋白产生,并提出了这是否可能增加患者对神经系统表现的易感性的问题。
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引用次数: 2
Polymorphisms in GLIS3 and susceptibility to diabetes mellitus: A systematic review and meta-analysis GLIS3多态性与糖尿病易感性:一项系统综述和荟萃分析
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100898
Guilherme Coutinho Kullmann Duarte , Tais Silveira Assmann , Bianca Marmontel de Souza , Daisy Crispim

The transcription factor Gli-similar 3 (GLIS3) has an important role in the development, survival and proliferation of pancreatic beta-cells and insulin gene expression regulation. Accordingly, genome-wide association studies have shown GLIS3 gene confers risk to both type 1 and type 2 diabetes mellitus (DM). However, data on the association of individual GLIS3 polymorphisms with DM are still inconclusive. Thus, this systematic review and meta-analysis was aimed to scrutinize the potential association between GLIS3 polymorphisms and DM. A literature search was carried out in EMBASE and PubMed resources to find all studies that analyzed GLIS3 polymorphisms regarding susceptibility to DM. Following the eligibility criteria, 25 studies were included in this systematic review. Twelve of them had complete data available, allowing meta-analyses (T1DM: 3 studies with rs7020673 polymorphism and 3 with rs10758593; T2DM: 6 with rs7034200 polymorphism and 3 with rs7041847). The rs7020673 and rs10758593 polymorphisms were not associated with T1DM. Regarding T2DM studies, the rs7041847A and the rs7034200C alleles were associated with risk for T2DM (OR = 1.08, 95% CI 1.00–1.16 and OR = 1.17, 95% CI 1.09–1.26; considering the allele contrast model). In conclusion, GLIS3 rs7034200 and rs7041847 polymorphisms seem to confer risk for T2DM. Additional studies are needed to confirm whether GLIS3 polymorphisms are associated with DM.

转录因子glis -similar 3 (GLIS3)在胰腺β细胞的发育、存活和增殖以及胰岛素基因表达调控中具有重要作用。因此,全基因组关联研究表明,GLIS3基因可增加1型和2型糖尿病(DM)的风险。然而,个体GLIS3多态性与糖尿病的关联数据仍然没有定论。因此,本系统综述和荟萃分析旨在仔细研究GLIS3多态性与糖尿病之间的潜在关联。我们在EMBASE和PubMed资源中进行了文献检索,以找到所有分析GLIS3多态性与糖尿病易感性的研究。根据入选标准,本系统综述纳入了25项研究。其中12项具有完整的可用数据,允许进行荟萃分析(T1DM: 3项rs7020673多态性研究和3项rs10758593多态性研究;T2DM: rs7034200多态性6例,rs7041847多态性3例。rs7020673和rs10758593多态性与T1DM无关。在T2DM研究中,rs7041847A和rs7034200C等位基因与T2DM风险相关(OR = 1.08, 95% CI 1.00-1.16和OR = 1.17, 95% CI 1.09-1.26);考虑等位基因对比模型)。总之,GLIS3 rs7034200和rs7041847多态性似乎增加了2型糖尿病的风险。GLIS3多态性是否与糖尿病相关还需要进一步的研究来证实。
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引用次数: 2
Interleukin-33 gene variants (rs928413, rs16924159 and rs7037276) and susceptibility to asthma among Iraqi adult patients 伊拉克成年患者白介素-33基因变异(rs928413、rs16924159和rs7037276)与哮喘易感性的关系
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100907
Semaa A. Shaban , Suad A. Brakhas , Ali H. Ad'hiah

Interleukin-33 is proposed to influence asthma susceptibility. Three IL33 gene variants (rs928413, rs16924159 and rs7037276) were included in a case-control study conducted on 104 Iraqi asthmatics and 111 controls. Tetra-primer-amplification-refractory-mutation-system-polymerase-chain-reaction method was used to determine these variants. Logistic regression analysis showed that A allele and AA genotype of rs928413 were significantly associated with an increased asthma risk under allele and recessive models, respectively. Regarding rs16924159, allele, recessive, dominant and codominant models demonstrated a significant association with asthma susceptibility, but the highest risk was found for AA genotype under recessive model. For SNP rs7037276, neither alleles nor genotypes were associated with asthma risk. Tri-locus haplotype analysis (in the order rs928413, rs16924159 and rs7037276) revealed that A-G-T haplotype frequency was significantly elevated in asthmatics compared to controls, while frequency of G-G-T haplotype was significantly decreased. In conclusions, two IL33 gene SNPs (rs928413 and rs16924159) were proposed to be associated with asthma susceptibility.

白细胞介素-33被认为影响哮喘易感性。3种IL33基因变异(rs928413、rs16924159和rs7037276)纳入了一项对104名伊拉克哮喘患者和111名对照者进行的病例对照研究。采用4 -引物-扩增-难解-突变-聚合酶链反应法测定这些变异。Logistic回归分析显示,rs928413的A等位基因和AA基因型在等位基因和隐性模型下分别与哮喘风险增加显著相关。rs16924159等位基因、隐性基因、显性基因和共显性基因模型与哮喘易感性均有显著相关性,但AA基因型在隐性模型下风险最高。对于SNP rs7037276,等位基因和基因型都与哮喘风险无关。三位点单倍型分析(顺序为rs928413、rs16924159和rs7037276)发现哮喘患者A-G-T单倍型频率显著高于对照组,G-G-T单倍型频率显著低于对照组。综上所述,两个IL33基因snp (rs928413和rs16924159)可能与哮喘易感性相关。
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引用次数: 2
Genetic and cytogenetic screening of autistic spectrum disorder: Genotype-phenotype profiles 自闭症谱系障碍的遗传和细胞遗传学筛查:基因型-表型谱
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100924
Arun Meyyazhagan , Balamuralikrishnan Balasubramanian , Haripriya Kuchi Bhotla , Murugesh Easwaran , Sureshkumar Shanmugam , Karthick Kumar Alagamuthu , Vijaya Anand Arumugam , Sasikala Keshavarao , Manikantan Pappusamy

Autism, a pervasive developmental disorder typically characterized by repetitive behaviour, social skills deficit (or a deficit in social communication), speech and language impairments. Our prime focus is to analyze the clinical features and phenotypical behavioural changes using the diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM IV-TR), and locating the biomarkers associated with specific autistic characters using karyotyping and fluorescence in situ hybridization (FISH) techniques. The prevalence rate of the neurexin 1 (NRXN1) gene polymorphism was also assessed in the current study. The study group involved 196 samples with 98 autistics, and equal age-matched (±2) controls based on their birth order and carrier. The participants include 35.2% males (n = 69) and 14.8% females (n = 29). The autistic and control participants were categorized based on their ages as group I (<12 yrs) with n = 62; males n = 41 (20.9%); females n = 21 (10.7%) and group II (≥12 yrs)-n = 36; males n = 28 (14.2%); females n = 08 (4.08%). Karyotyping was done for autism participants (n = 98) and the results showed that 90% of autistic participants were either the only child or the first child with a low perception and frequency in both the groups. Subsequently, we carried out the FISH assay on participants (n = 37) with higher DSM-IV TR score (≥30). Only 30 FISH tests were negative for subtelomeric deletions with NRXN1 polymorphism genotypic frequency as 62.50%, 25% and 25% for A/A, A/G and G/G genotype respectively. Our study suggests the link between a haplotype with clinical signs of autism for the single nucleotide sequence (SNP rs9636391) and links autistic characters and gene among autistic children according to their birth order, age and gender in India.

自闭症,一种普遍的发育障碍,典型特征是重复行为、社交技能缺陷(或社交沟通缺陷)、言语和语言障碍。我们的主要重点是使用精神障碍诊断和统计手册,第四版,文本修订(DSM IV-TR)分析临床特征和表型行为变化,并使用核型和荧光原位杂交(FISH)技术定位与特定自闭症特征相关的生物标志物。本研究还评估了神经rexin 1 (NRXN1)基因多态性的患病率。研究小组包括196个样本,98个自闭症患者,以及根据出生顺序和携带者年龄匹配(±2)的对照组。参与者中男性占35.2% (n = 69),女性占14.8% (n = 29)。自闭症组和对照组根据年龄分为I组(12岁),n = 62;男性41例(20.9%);女性21例(10.7%),II组(≥12岁)36例;男性28例(14.2%);女性n = 08(4.08%)。对自闭症参与者(n = 98)进行了核型分析,结果显示90%的自闭症参与者要么是独生子女,要么是第一个孩子,两组的感知能力和频率都很低。随后,我们对DSM-IV TR评分较高(≥30)的参与者(n = 37)进行FISH检测。A/A、A/G和G/G基因型的NRXN1多态性亚端粒缺失阳性率分别为62.50%、25%和25%,FISH检测结果为阴性。我们的研究表明,单倍型与自闭症临床症状之间存在单核苷酸序列(SNP rs9636391)的联系,并根据印度自闭症儿童的出生顺序、年龄和性别将自闭症特征和基因联系起来。
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引用次数: 0
Associations of INPPL1 (+1893CC/AA and + 2945AA/GG) exonic polymorphisms with the risk of type 2 diabetes mellitus in North Indian population: A case control study INPPL1(+1893CC/AA和+2945AA/GG)外显子多态性与北印度人群2型糖尿病风险的相关性:一项病例对照研究
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100929
Jaswinder Singh , Vikas Kumar , Kiran Bala , Ashish Aneja , Jasbir Singh

Background and aim

INPPL1 gene encodes a lipid phosphatase Src homology 2-containing 5′-inositol phosphatase 2 (SHIP2) which is involved in the negative regulation of insulin signaling. In the light of several association studies of INPPL1 gene polymorphisms with T2DM, and the absence of association studies from India, present study was conducted to assess the association of two SNPs of INPPL1 gene with T2DM risk in North Indian population.

Material and method

Two single nucleotide polymorphism (SNPs) (+1893CC/AA and + 2945AA/GG) in INPPL1 gene were genotyped in total of 270 subjects with PCR-RFLP genotyping method.

Results

It was observed that, out of the two SNPs, only +1893CC/AA was found to be significantly associated with T2DM and frequency of A allele (C vs A, p = 0.002) has been found to be significantly higher in T2DM cases. Strong linkage disequilibrium was observed between two SNPs as assessed through D′ and r2 (D′ = 0.984, r2 = 0.009) and AG haplotype (OR = 3.59, 95% CI (1.59–9.80), p = 0.0015) was associated with increased risk of T2DM while CG haplotype (OR = 0.54, 95% CI (0.33–0.88) p = 0.012) significantly decreases the risk of developing T2DM. Regression analysis showed that SNP +1893CC/AA is associated with T2DM risk when adjusted for clinical/demographic variables.

Conclusion

Results showed that INPPL1 gene polymorphism +1893CC/AA may increase susceptibility to T2DM and ‘A' allele might be serving as a risk factor in development of T2DM in Indian population.

背景和目的:ppl1基因编码脂质磷酸酶Src同源2-含5 ' -肌醇磷酸酶2 (SHIP2),参与胰岛素信号的负向调控。鉴于已有几项关于INPPL1基因多态性与T2DM的关联研究,而印度缺乏相关研究,本研究旨在评估印度北部人群中INPPL1基因的两个snp与T2DM风险的关系。材料与方法采用PCR-RFLP基因分型方法对270例受试者进行INPPL1基因2个单核苷酸多态性(+1893CC/AA和+ 2945AA/GG)分型。结果2个snp中,只有+1893CC/AA与T2DM显著相关,而A等位基因的频率(C vs A, p = 0.002)在T2DM患者中显著较高。通过D′和r2 (D′= 0.984,r2 = 0.009)和AG单倍型(OR = 3.59, 95% CI (1.59-9.80), p = 0.0015)与T2DM发病风险增加相关,而CG单倍型(OR = 0.54, 95% CI (0.33-0.88) p = 0.012)显著降低T2DM发病风险。回归分析显示,在调整临床/人口统计学变量后,SNP +1893CC/AA与T2DM风险相关。结论INPPL1基因多态性+1893CC/AA可能增加印度人群对T2DM的易感性,“A”等位基因可能是印度人群发生T2DM的危险因素。
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引用次数: 1
Human leukocyte antigens (HLA) association with myasthenia gravis (MG) and its myasthenia manifestations in Algerian patients 人白细胞抗原(HLA)与阿尔及利亚重症肌无力(MG)及其重症肌无力表现的关系
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100937
Bouchtout Mohamed Nadji , Meçabih Fethi , Mihoubi Esma , Boukadir Chahrazad , Attal Elias , Daoudi Smail , Touil-Boukoffa Chafia , Raache Rachida , Attal Nabila

Background

Myasthenia gravis (MG) is an autoimmune disease with a well-established involvement of genetic factors.

Aim

this study was to assess the human leukocyte antigens (HLA) genes association with myasthenia gravis and its myasthenic manifestations.

Methods

We performed a case-control study where twenty eight patients and one hundred and nine healthy subjects were included. A subgroup of generalized and acetylcholine receptor antibodies positive myasthenia gravis was examined for myasthenic manifestations associations. HLA genotyping was performed by polymerase chain reaction- sequence specific oligonucleotide (PCR-SSO) method.

Results

On one hand, HLA A*30 and DRB1*04 alleles were more frequent among patients with myasthenia gravis whereas A*02 and B*49 were less frequent (p < 0.05). On the other hand, B*08 was positively associated with limb muscles weakness and negatively association with dysphagia while B*44 and DRB1*03 were both positively associate with cervical muscles weakness (p < 0.05).

Conclusion

Our results suggest the association of various HLA alleles with myasthenia gravis and some of its myasthenic manifestations. However, further studies are required support these findings and clarify the underlying mechanisms.

背景重症肌无力(MG)是一种与遗传因素相关的自身免疫性疾病。本研究旨在探讨人白细胞抗原(HLA)基因与重症肌无力及其症状的相关性。方法采用病例对照研究,纳入28例患者和109名健康受试者。重症肌无力亚群的广泛性和乙酰胆碱受体抗体阳性检查重症肌无力的表现关联。HLA基因分型采用聚合酶链反应-序列特异性寡核苷酸(PCR-SSO)法。结果重症肌无力患者HLA A*30、DRB1*04等位基因较多,A*02、B*49等位基因较少(p <0.05)。另一方面,B*08与肢体肌无力呈正相关,与吞咽困难呈负相关,而B*44和DRB1*03与颈肌无力均呈正相关(p <0.05)。结论多种HLA等位基因与重症肌无力及其部分症状有关。然而,需要进一步的研究来支持这些发现并阐明潜在的机制。
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引用次数: 0
Association of methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes promoter methylation pattern with the risk of essential hypertension 亚甲基四氢叶酸还原酶(MTHFR)和胱硫氨酸β合酶(CBS)基因启动子甲基化模式与原发性高血压风险的关联
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100914
Shabnaz Koochakkhani , Fatemeh Nabizadeh , Azim Nejatizadeh , Ebrahim Eftekhar

Methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) are key enzymes in the metabolism of homocysteine pathway whose dysfunction can lead to essential hypertension (EH). This study aimed to investigate the possible association of MTHFR and CBS genes promoter methylation patterns with the risk of EH. We also aimed to search differentially expressed microRNAs (miRs) and demonstrate the role of miRs in the aberrant DNA methylation in essential hypertensive patients by targeting DNA methyltransferases (DNMTs).

20 essential hypertensive patients and 20 healthy controls were selected. DNA methylation levels of 10 CpG dinucleotides on MTHFR and 19 CpG dinucleotides on CBS genes promoter was measured using Bisulfite-Sequencing PCR (BSP). The GSE118578 profile was downloaded from the GEO database to identify differentially expressed miRs in hypertensive patients and R statistical software was used to analyze the data. Enrichment analysis was conducted to predict target genes using databases of Targetscan, and miRDB-MicroRNA Target Prediction Database.

No significant association between MTHFR gene methylation and EH was observed. There was a significant association between one of the CpG sites of CBS gene promoter (CpG19 (+1035C)) and EH [OR = 5.3(0.895–31.393), p = 0.047]. Furthermore, we reported a list of miRs that may have an essential role in regulating DNA methylation by targeting DNMTs.

Our findings showed that hypermethylation of CpG19 (+1035C) of CBS gene promoter could increase the risk of EH. Methylation status of MTHFR gene had no significant association with EH. Also, in-silico investigation showed that miRs may affect aberrant genes methylation through altering DNMTs biogenesis.

亚甲基四氢叶酸还原酶(MTHFR)和胱硫氨酸β合酶(CBS)是同型半胱氨酸通路代谢的关键酶,其功能障碍可导致原发性高血压(EH)。本研究旨在探讨MTHFR和CBS基因启动子甲基化模式与EH风险的可能关联。我们还旨在寻找差异表达的microRNAs (miRs),并通过靶向DNA甲基转移酶(dnmt)来证明miRs在原发性高血压患者异常DNA甲基化中的作用。选取原发性高血压患者20例,健康对照20例。采用亚硫酸盐测序PCR (bisulte - sequencing PCR, BSP)检测了MTHFR上10个CpG二核苷酸和CBS基因启动子上19个CpG二核苷酸的DNA甲基化水平。从GEO数据库下载GSE118578基因图谱,识别高血压患者差异表达的miRs,并使用R统计软件对数据进行分析。利用Targetscan和miRDB-MicroRNA靶基因预测数据库进行富集分析预测靶基因。MTHFR基因甲基化与EH无显著相关性。CBS基因启动子CpG位点之一CpG19 (+1035C)与EH有显著相关性[OR = 5.3(0.895-31.393), p = 0.047]。此外,我们报道了一系列miRs,这些miRs可能通过靶向dnmt在调节DNA甲基化中发挥重要作用。结果表明,CBS基因启动子CpG19 (+1035C)的高甲基化可增加EH的风险。MTHFR基因甲基化状态与EH无显著相关性。此外,计算机研究表明,miRs可能通过改变dnmt的生物发生来影响异常基因的甲基化。
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引用次数: 0
Genetic association of DISC1 variant rs3738401 with susceptibility to Schizophrenia risk in North Indian population 北印度人群中DISC1变异rs3738401与精神分裂症易感性的遗传关联
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100923
Indu Priya , Isar Sharma , Sakshi Sharma , Suruchi Gupta , Manu Arora , G.H. Rasool Bhat , Ritu Mahajan , Nisha Kapoor

DISC1 regulates signalling pathways which are involved in neuronal development, brain maturation like neuronal proliferation and processes involved in central nervous system development. The DISC1 gene is one of the potential candidate gene involved in Schizophrenia risk. In the present study, we performed case-control association study using TaqMan based chemistry in which a total of 382 individuals, 152 Schizophrenia patients and 230 healthy controls were genotyped to explore the association of rs3738401 and rs16854954 of DISC1 gene with susceptibility to Schizophrenia risk in North Indian population of Jammu region. The findings from the study revealed that rs3738401 was significantly associated with Schizophrenia and the G allele of rs3738401 is associated with increased risk for the disorder (OR = 1.66; [1.22–2.24 at 95%CI] P = 0.001) whereas other variant rs16854954 of DISC1 gene was not found to be associated with the disease(OR = 0.96, [0.71–1.30 at 95% CI] P = 0.75). The present study offers an important evidence on the genetic cause of DISC1 gene in North Indian population and further strengthens the GWAS findings on the role of DISC1 in schizophrenia risk. This study provides the holistic view about the Schizophrenia in Jammu region, North Indian population and it can be a hallmark if verified on a very large sample size (cohort).

DISC1调节参与神经元发育、脑成熟如神经元增殖和中枢神经系统发育过程的信号通路。DISC1基因是与精神分裂症风险相关的潜在候选基因之一。本研究采用TaqMan化学方法对382名个体、152名精神分裂症患者和230名健康对照进行了病例对照关联研究,探讨了查谟地区北印度人群中DISC1基因rs3738401和rs16854954与精神分裂症易感性的关系。研究结果显示,rs3738401与精神分裂症显著相关,rs3738401的G等位基因与精神分裂症风险增加相关(OR = 1.66;[1.22-2.24, 95%CI] P = 0.001),而DISC1基因的其他变异rs16854954未被发现与疾病相关(OR = 0.96, [0.71-1.30, 95%CI] P = 0.75)。本研究为北印度人群中DISC1基因的遗传原因提供了重要证据,并进一步加强了GWAS关于DISC1在精神分裂症风险中的作用的研究结果。这项研究提供了关于查谟地区精神分裂症的整体观点,北印度人口,如果在一个非常大的样本量(队列)上得到验证,它可以成为一个标志。
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引用次数: 0
Novel association of PhosphoSerine PHosphatase (PSPH) gene mutations with male infertility identified through whole exome sequencing of South Indians 通过南印度人的全外显子组测序确定了磷酸丝氨酸磷酸酶(PSPH)基因突变与男性不育的新关联
IF 0.7 Q4 GENETICS & HEREDITY Pub Date : 2021-09-01 DOI: 10.1016/j.mgene.2021.100897
Golnaz Shemshaki , Mohsen Najafi , Ashitha S. Niranjana Murthy , Suttur S. Malini

Male infertility (MI) is mainly caused by spermatogenic failure, and despite long years of assisted reproductive therapy, a significant number of cases remain idiopathic. Oligoasthenozoospermia (OA) is one of the most severe idiopathic MI forms, conditioned with decreased sperm motility and count. However, its pathology remains unclear, but few genetic factors have been identified. The main aim of this study was to find genetic variations in spermatogenic genes with severe OA. Semen and blood samples were collected from 250 MI subjects. Semen analysis, karyotyping, and Y microdeletion was performed to retain purely idiopathic MI cases (n = 247). 40 OA cases were identified, of which four severe cases were subjected to whole-exome sequencing, bioinformatics analyses, and pathway analysis, followed by validation of pathogenic variants in the remaining 36 OA cases through Sanger sequencing. We identified six variants in exon5 of gene PSPH, of which four variants were predicted to be pathogenic and two damaging mutations in exon4. In this study, we propose the novel role of the PSPH gene in their different mechanistic pathways. Detailed pathway analysis of enzyme PSPH involved in l-serine biosynthesis demonstrated that its dysfunction could cause a decrease in sperm count and sperm motility. The hypothesized function of PSPH in eliciting OA has been described.

男性不育症(MI)主要由生精失败引起,尽管经过多年的辅助生殖治疗,但仍有相当数量的病例是特发性的。少弱精子症(OA)是最严重的特发性心肌梗死形式之一,以精子活力和数量减少为条件。然而,其病理尚不清楚,但很少有遗传因素已确定。本研究的主要目的是发现严重OA患者生精基因的遗传变异。收集了250例心肌梗死患者的精液和血液样本。进行精液分析、核型分析和Y微缺失以保留纯粹特发性心肌梗死病例(n = 247)。共发现40例OA病例,其中4例重症病例进行全外显子组测序、生物信息学分析和通路分析,其余36例OA病例通过Sanger测序验证致病变异。我们在PSPH基因外显子5中发现了6个突变,其中4个突变被预测为致病性突变,2个突变被预测为破坏性突变。在这项研究中,我们提出了PSPH基因在它们不同的机制途径中的新作用。对参与l-丝氨酸生物合成的PSPH酶的详细途径分析表明,其功能障碍可能导致精子数量和精子活力下降。PSPH在引发OA中的假设功能已被描述。
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Meta Gene
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