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1.
Arq. bras. cardiol ; 119(4): 593-601, Oct. 2022. tab
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1403367

ABSTRACT

Resumo Fundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.


Abstract Background It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

2.
J Indian Med Assoc ; 2022 Sept; 120(9): 12-16
Article | IMSEAR | ID: sea-216600

ABSTRACT

Background: Chronic HBV (CH) infection and its consequences including cirrhosis (C) and Hepatocellular Carcinoma (HCC) still represent a major Global health. The relationship between HCC and various mutations of HBx gene has been reported. In the present study, we aimed to determine the sequence variation of HBx gene in patients with Chronic HBV infection or C/HCC. Materials and Methods : In this cross-sectional study, 15 patients with HBV chronic infection and 13 with C/HCC were included. After viral DNA extraction using commercial kit HBX gene was amplified using an in-house nestedPCR. Then, bi-directional sequencing was performed on the PCR product. The data resulting from sequencing were aligned with reference HBV sequence to identify the mutations. Results : The mean age of CH and C/HCC groups was 38.23�.46 and 50.67�.22 years old, respectively. We found 43 and 20 Amino acid substitutions inside the region of 88�4 from HBx protein in CH and C/HCC groups, respectively. In addition, K130M+V131I mutation was found in 13.34% (2/15) and 30.7% (4/13) of patients in the CH and C/HCC groups, respectively (P=0.36). Furthermore, 10 deletion mutations were observed in both groups with no significant difference (P=0.8). Conclusion : The results of the present study indicated the relatively high frequency of Amino acid substitutions and deletion, especially in part of region 88-154 from HBx Protein in patients with CH and C/HCC. The findings should be considered in a larger population

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