RESUMEN
Cerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase ( MTHFR ), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase ( MS ), and the A192G(rs662) of paraoxonase 1( PON1 ) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme ( ACE ) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.
RESUMEN
Homocysteine and its modulating genes have strongly emerged as novel biomarkers for coronary artery disease (CAD). In the present study, we investigated whether polymorphisms in homocysteine pathway genes and the plasma levels of homocysteine, folate, and vitamin B12, independently or in combination, are associated with CAD risk. A total of 504 participants were recruited (cases, n = 254; controls, n = 250, respectively). Tetra primer allele refractory mutation system polymerase chain reaction (PCR) was used for resolving the genotypes of 5'10' methylenetetrahydrofolate reductase 'MTHFR' polymorphisms (rs1801133, rs1801131), 5' methyl tetrahydrofolate homocysteine methyltransferase 'MTR' polymorphism (rs1805087), paroxanse1 'PON1' polymorphism (rs662), and cystathionine beta synthase 'CBS' polymorphism (rs5742905). Conventional PCR amplification was carried out for resolving angiotensin converting enzyme 'ACE' insertion/deletion (I/D) polymorphism (rs4646994). ANOVA analysis, adjusted for the covariates, revealed that rs1801133, rs1805087 polymorphisms and homocysteine levels were associated with CAD. Logistic regression analysis (adjusted) revealed similar findings. Logistic regression analysis after applying factorial design to the studied single nucleotide polymorphisms (SNPs) revealed that homocysteine levels and heterozygous and mutant alleles at rs1801133, rs1805087, along with mutant alleles at rs1801131, rs4646994, conferred higher risk for CAD. Our results provide insight into the multifactorial nature of coronary artery disease. We highlight that SNPs in folate pathway genes and homocysteine have role in disease causation and can be used in disease prediction strategies.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Enfermedad de la Arteria Coronaria/genética , Hiperhomocisteinemia/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo de Nucleótido Simple , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/enzimología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hiperhomocisteinemia/diagnóstico , Hiperhomocisteinemia/enzimología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
A 25-year-old woman, later identified as index case of Crimean-Congo hemorrhagic fever (CCHF), presented to Holy Family Hospital in Rawalpindi, Pakistan with fever and generalized coagulopathy. A retrospective contact tracing was conducted to explore the modes of exposure possibly associated with transmission of CCHF infection among contacts. We traced 32 contacts of the index case and 158 contacts of secondary cases and tested them for IgG and IgM antibodies against CCHF virus by an enzyme-linked immunosorbent assay technique. According to the type of exposure, contacts were divided into five subsets: percutaneous contact with blood, blood contact to unbroken skin, cutaneous contact to non-sanguineous body fluids, physical contact with patients without body fluids contact, and close proximity without touching. Two out of four contacts who reported percutaneous exposure tested positive for antibodies to CCHF virus. We conclude that simple barrier methods and care in provision of CCHF cases may prevent transmission of this infection.
Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica de Crimea/epidemiología , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Pakistán/epidemiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de RiesgoRESUMEN
A nosocomial outbreak of Crimean-Congo hemorrhagic fever occurred in Rawalpindi, Pakistan in February 2002. The identified index case died shortly after admission to a hospital. Two of the health care workers became secondary cases; one of them died on day 13 after coming in contact with the index case. The other secondary case was successfully treated with oral ribavirin.