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Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.

BACKGROUND: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD). METHODS: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study.

XP-A cells complemented with Arg228Gln and Val234Leu polymorphic XPA alleles repair BPDE-induced DNA damage better than cells complemented with the wild type allele.

Functional effects of Arg228Gln and Val2343Leu XPA polymorphisms on benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide-(+/-)-anti (BPDE) survival and repair were investigated in SV40 immortalized XP12RO cells complemented with wild type and polymorphic XPA cDNAs in an inducible cDNA expression system. In contrast to previous studies showing little impact of XPA polymorphisms on UV survival and repair, cells complemented with polymorphic XPAs displayed improved BPDE survival and repair as compared to wild type XPA-complemented cells. Survival after BPDE treatment was measured using AlamarBlue re

Branched chain acyltransferase absence due to an Alu-based genomic deletion allele and an exon skipping allele in a compound heterozygote proband expressing maple syrup urine disease.

Branched chain alpha-ketoacid dehydrogenase assembles around a core of the acyltransferase components on the matrix side of the mitochondrial inner membrane. Autosomal recessive mutations in humans are known to decrease the function of this complex resulting in the clinical phenotype of maple syrup urine disease. Within this wide group of mutations are a subset which result in the antigenic absence of the acyltransferase protein of the complex. Here we describe two mutations in a compound heterozygote proband which result in this acyltransferase-negative phenotype. The mutant allele inherited

Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele.

Infantile-onset glycogen storage disease type II, or Pompe disease, results from a genetic deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Sequencing of the cDNA from a cell line (GM 244) derived from a patient with Pompe disease demonstrated a T953-to-C transition that predicted a methionine-to-threonine substitution at codon 318. The basepair substitution resulted in loss of restriction-endonuclease sites for NcoI and StyI. Analysis of genomic DNA revealed both a normal and an abnormal NcoI fragment, indicating that the patient was a genetic compound. NcoI and StyI digestion

HLA Class II Alleles Are Associated With Anti-Drug Antibodies in Ulcerative Colitis Patients Treated With Etrolizumab.

Patients treated with etrolizumab, a monoclonal antibody drug for ulcerative colitis, often develop anti-drug antibodies (ADA) and neutralising antibodies (NAb). To investigate genetic risk factors, we evaluated associations between HLA alleles and ADA/NAb development. HLA-DQB1*06:03 demonstrated the most significant association with both ADA (OR = 7.3, p ≤ 7.6 × 10-13) and NAb (OR = 13.1, p ≤ 7.7 × 10-13). After controlling for HLA-DQB1*06:03, HLA-DQA1*03:03 emerged as the next most significant allele associated with ADA (OR = 2.8, p ≤ 1.0 × 10-3) and NAb (OR = 5.0, p ≤ 1.3 × 10-3). Notably, …

CYP2C19 loss-of-function alleles and early neurological deterioration in minor ischemic stroke receiving dual antiplatelet therapy.

OBJECTIVE: Early neurological deterioration (END) is a common complication after acute ischemic stroke (AIS). Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is widely used in selected patients with minor ischemic stroke (MIS) to reduce early recurrent ischemic events. This study aimed to investigate the incidence of END in patients with MIS receiving DAPT and explore factors associated with END. METHODS: We performed a single-center retrospective cohort study including consecutive cases of MIS treated with DAPT. END was defined as an increase of ≥2 points in the NIHSS score fro

HLA-DRB1*03 and HLA-DRB1*04 alleles in patients infected with dengue virus in Burkina Faso.

INTRODUCTION: Dengue fever is a viral disease transmitted by mosquitoes of the genus Aedes. It is a major public health issue in tropical and subtropical areas. In West Africa, the most prevalent dengue virus (DENV) serotypes are DENV-1 and DENV-2, which are responsible for the majority of epidemics on the continent. In addition to environmental factors, genetics, including HLA class II alleles, could influence susceptibility or protection against disease. AIMS OF STUDY: This study aimed to characterize HLA-DRB1*03 and HLA-DRB1*04 alleles in dengue patients, exploring their association with s…

Antiretroviral therapy blocks natural selection on protective and disease-susceptible HLA-B alleles in HIV-1 infection.

MHC polymorphism is explained by natural selection driven by the MHC-dependent impact of certain infections, inflammatory conditions, autoimmune diseases, and cancers. However, examples of human disease driving this process are rare. We evaluated the impact of HIV-1 in altering HLA-I frequencies in KwaZulu-Natal, South Africa, and the influence of antiretroviral therapy (ART) on this process. In a historical mother-child cohort in the pre-ART era (1998-2005), HIV-1 survival and vertical transmission were both strongly HLA-B dependent: "disease-susceptible" HLA-B alleles (HLA-B*18/B*45:01/B*58:…

Adult-Onset Recessive Cerebellar Ataxia and Severe Multisystem Disease-Associated Genes: Hypomorphic Alleles and Clinical Interpretation Pitfalls.

BACKGROUND: Adult-onset recessive cerebellar ataxias remain frequently unresolved after next-generation sequencing, partly because phenotype-driven filtering can deprioritize biallelic variants in genes historically associated with severe pediatric multisystem disease. This review examines how attenuated, hypomorphic, or residual-function genotypes may present as late-onset, cerebellar-predominant disease and aims to support clinical interpretation of apparently discordant recessive findings. METHODS: We performed a narrative, pathway-based synthesis of autosomal recessive adult- or late-onse

Association of C4 Null Alleles and Persistently Low C4 in Asian Indian Patients With Systemic Lupus Erythematosus.

The association between heterozygous C4 deficiency and systemic lupus erythematosus (SLE) is unclear. There is a lack of data in South Asian Indians on any possible association of C4A and C4B null alleles with lupus. We aimed to study the prevalence of C4A and C4B null alleles in a cohort of SLE patients with persistently low C4 levels compared to healthy controls (HC). Patients with SLE and HC were recruited for this prospective observational study. C4 (C4AQ and C4BQ) polymorphisms were tested using a touch-down polymerase chain reaction protocol. One hundred and three SLE patients and 103 HC…

Библиометрический анализ исследований в области контроля за конкретными случаями, касающихся связи между аллеями АВП и множественным склерозом у взрослых.

Множественный склероз (MS) представляет собой сложное аутоиммунное заболевание, которое влияет на центральную нервную систему (CNS), при этом генетические и экологические факторы играют важную роль в ее развитии и развитии. Одним из наиболее важных генетических факторов, связанных с MS, является генный комплекс HLA. Взаимосвязь между ВУЗом и МЗ стала предметом многочисленных исследований, однако до настоящего времени не сообщалось о результатах библиометрического анализа этих исследований. Поэтому цель этого исследования состояла в том, чтобы дать всеобъемлющий обзор выпуска публикаций, влияни

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease that affects the central nervous system (CNS) with genetic and environme … ong researchers and institutions, with the most common research topics being the association of HLA alleles with MS susceptibility, disease course, and treatment response. This study's limitations stem from the inherent biases associated with bibliometric analysis, including database and coverage bias, citation bias, and biases related to accessibility an …

MHC-I выступает посредником по разминированию и антителной реакции на зоонотический вирус Ласса в грызунах Мастомиса.

Западноафриканские грызуны мастомики являются основным резервуаром зоонотического вируса Ласса (LASV). Вирус вызывает геморрагическую лихорадку Ласса и значительную смертность у людей. До настоящего времени роль иммуногенетики Мастомии в устойчивости и стойкости ЛАГВ в значительной степени неизвестна. Здесь мы изучили роль I класса I (MHC-I) < < Большой гистокомпьютерный комплекс > > в связи с инфекцией ЛАГ (т.е. активная и очищенная инфекция, определяемая с помощью ПЦР и анализа иммунной флюоресценции на антителах IGG, соответственно) в Мастомисе Натененсисе и М. Эритролюкусе, ото

Совпадение в аннотации оригинала
West African Mastomys rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and co … and M. erythroleucus sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in M. natalensis and M. erythroleucus, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In M. natalensis, the MHC allele ManaMHC-I*006 was negativ …

Hidden prevalence of deletion-inversion bi-alleles in CRISPR-mediated deletions of tandemly arrayed genes in plants.

Tandemly arrayed genes (TAGs) with functional redundancy and chromosomal linkage constitute 14 ~ 35% in sequenced plant genomes. The multiplex CRISPR system is the tool of choice for creating targeted TAG deletions. Here, we show that up to ~80% of CRISPR-mediated TAG knockout alleles in Arabidopsis and rice are deletion-inversion (delinver) bi-alleles, which are easily misidentified as homozygous deletion alleles by routine PCR-based genotyping. This can lead to misinterpretation of experimental data and production of progenies with genetic heterogeneity in an unnoticed manner. In ~2,650 tran…

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

BACKGROUND: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol … been described (CH-1 to CH-9). AIMS: The aim of this study was to genetically evaluate two variant alleles carried by a 22-year-old female with the non-salt-wasting simple virilizing form of CAH and biallelic 30-kb deletions. METHODS: The haplotypes of the CYP21A2 heterozygous variants, as well as the chimeric junction sites, were determined by Sanger s …

Expression analysis of NF1-mutated alleles in a rare compound heterozygous spinal NF1 patient by digital PCR.

BACKGROUD: Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder. Spinal neurofibromatosis (SNF) is a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal nerve roots. Although both forms are caused by intragenic heterozygous variants of NF1, missense variants have been associated with SNF, according to a dominant inheritance model causing haploinsufficiency. Most patients carry pathogenic variants in one of the NF1 alleles; nevertheless, patients with both NF1-mutated copies have been described. Interestingly, all NF1 variants carr…

На подверженность оккультному гепатиту В у населения Западной Африки влияют аллели, подобные иммуноглобулиновым клеткам рецептора.

Заражение окультным гепатитом В (ОБИ) является проблемой здравоохранения в Буркина-Фасо. ОБИ представляет собой фактор риска для развития цирроза и гепатоклеточной карциномы (ГК). ОБИ может быть вызвано мутантными вирусами, которые не поддаются обнаружению с помощью анализа HBsAg, или сильным подавлением вирусного репликации и генного экспрессии под давлением иммунной системы принимающей страны. Изучение роли геномных полиморфизмов клеточного иммуноглобулинового типа (КИР) у пациентов Буркина-Фасо с ОБИ в сравнении со здоровыми и хроническими гепатитами В. В общей сложности было набрано 286 уч

Relationships between Mitochondrial Function, AMPK, and TORC1 Signaling in Lymphoblasts with Premutation Alleles of the FMR1 Gene.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5' region that, in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines …

Genomic diversities of ctxB, tcpA and rstR alleles of Vibrio cholerae O139 strains isolated from Odisha, India.

The genome of Vibrio cholerae O139 strains has undergone cryptic changes since its first emergence in 1992 in South India. This study aimed to determine the presence of genotypic changes marked in ctxB, tcpA and rstR genes located within the CTX prophages among the strains of V. cholerae O139 isolated from 1999 to 2017 in Odisha. Antibiotic susceptibility test was conducted on 59 V. cholerae O139 strains. A conventional PCR assay was done for ctxB gene typing followed by sequencing along with identification of rstR and tcpA gene. Pulsed-field gel electrophoresis (PFGE) was carried out to revea

Novel missense alleles of SIGMAR1 as tools to understand emerin-dependent gene silencing in response to cocaine.

UNLABELLED: Sigma-1 receptor (Sigma1R; SIGMAR1), an integral membrane protein of the endoplasmic reticulum and nuclear envelope, has a hydro … er nuclear lamina function in brain or other tissues. We examined the frequency of SIGMAR1 missense alleles among 60,706 unrelated individuals in the ExAC database. We identified two novel SIGMAR1 missense variants of particular interest due to their frequency and potential to impact molecular association with emerin or other nuclear lamina proteins. Vari …

The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer.

BACKGROUND: DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. OBJECTIVE: The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles. METHOD: The allelic variants were iden…