Analysis of 14 genetic polymorphisms for risk factors in Malaysian essential hypertension with or without type 2 diabetes mellitus subjects

Objectives The objective of this study was to determine the association of insertion/deletion (I/D), G2350A and T3892C polymorphisms of angiotensin converting enzyme (ACE) gene, A20C and A6G polymorphism of angiotensinogen (AGT) gene, BglI and MboI polymorphisms of renin gene, I/D of alpha 2B adrenoceptor gene, Gly460Trp of aldosterone synthase gene, Lys173Arg of adducin gene, A6244G polymorphism of the insulin receptor gene, S477X polymorphism of the lipoprotein lipase gene, C511T polymorphism of the interleukin gene and C825T polymorphism of the G protein beta 3 subunit (GNβ3) gene in essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM) of Malaysian subjects. Methods This cross-sectional study includes 70 EHT without T2DM, 65 EHT with T2DM and 75 unrelated healthy control subjects. Genomic DNA was extracted from the peripheral blood. The polymerase chain reaction (PCR)-restriction fragment length polymorphism, mutagenically PCR and the hot-start PCR methods were carried out to detect the genotypes of the various genetic polymorphisms. All the PCR products and the restricted fragments were resolved electrophoretically on agarose and polyacrylamide gels. Statistical analyses was done using SPPS version 14.0. Results Among the 14 genetic polymorphisms, only I/D and G2350A polymorphism of ACE gene, I/D polymorphism of alpha adrenoceptor gene and A6G variant of AGT gene differed significantly (p0.05) when compared to control subjects. Conclusions The alleles of I/D and G2350A polymorphisms of ACE, A6G of AGT and I/D of alpha 2B adrenoceptor genes can be considered as possible genetic markers or predisposing risk factors for EHT with or without T2DM in Malaysian subjects

Analysis of partial AZFc deletions in Malaysian infertile male subjects

Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions

C-511T polymorphism of interleukin-1 β gene is not associated in type 2 diabetes mellitus - a study in Malaysian population.

The objective of this study is to determine the association between the C-511T polymorphism of Interleukin -1 β gene in T2DM with or without hypertension in Malaysian population. A total of 175 subjects were recruited for this study. Genotyping of C-511T variant was performed by Hot-start PCR-RFLP analysis. The frequency for CC, TC and TT genotypes of C-511T variant in IL-1 β gene was 25.45, 40 and 34.55% in T2DM 25, 51.67 and 23.33% in T2DM with hypertension and 21.66, 36.67 and 41.67% respectively found in controls (p>0.05). This study suggests that there was no significant difference in the genotypic distribution of C-511T polymorphism of IL-1 β gene between T2DM and controls. Therefore, C-511T variant in IL-1 β gene polymorphism is not considered an independent risk factor or not a predictor for T2DM in Malaysian population

Acute necrotising pancreatitis and acalculous cholecystitis: a rare presentation of leptospirosis

Leptospirosis typically presents with fever and thrombocytopenia, with or without jaundice. Acute necrotising pancreatitis and acalculous cholecystitis are rare presentations of this spirochetal infection. Here is the case of necrotising pancreatitis and acalculous cholecystitis associated with leptospirosis in an elderly patient. Leptospirosis was diagnosed by serological tests and abdominal CT imaging. The patient was successfully treated medically with intravenous antibiotics (imipenem and ceftriaxone) and proper hydration

Analysis of human bradykinin receptor gene and endothelial nitric oxide synthase gene polymorphisms in end-stage renal disease among Malaysians

The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R) in Malaysian end-stage renal disease (ESRD) subjects. A total of 150 ESRD patients were recruited from the National Kidney Foundation’s (NKF)dialysis centers in Malaysia and compared with 150 normal healthy individuals. Genomic DNA was extracted from buccal cells of all the subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was carried out to amplify the products and the restricted fragments were separated by agarose gel electrophoresis. Statistical analyses were carried out using software where a level of p T, 4b/a) and eNOS gene (c.894G>T) polymorphisms were not statistically significant (p >0.05) when compared to the control subjects. The B2R and eNOS gene polymorphisms may not be considered as genetic susceptibility markers for Malaysian ESRD subjects

Analysis of homocysteine metabolism enzyme gene polymorphisms in non-syndromic congenital heart disease patients among Malaysians

Congenital heart disease (CHD) mainly is caused by the incomplete development of the heart during the first 6 weeks of pregnancy. Chromosomal and genetic abnormalities in the child and high levels of homocysteine in the blood are some of the risk factors related to CHD. Several studies in various populations have been done to determine the candidate genes in the predisposition to CHD with contradictory results, but there have been no studies that had been found in Malaysian CHD patients on homocysteine gene polymorphisms. Hence, this study was conducted to determine the allelic and genotypic analysis of the polymorphisms in candidate genes of the homocysteine enzymes; Methylenetetrahydrofolate Reductase (MTHFR), Cystathionine-b-synthase (CBS), Methionine Synthase (MTR) and Methionine Synthase Reductase (MTRR) genes. Based on the inclusion and exclusion criteria, buccal or blood samples were collected from 150 Malaysian non-syndromic CHD patients and 150 samples from healthy subjects as controls with no matching of age, genders and race between cases and controls. Genomic DNA was extracted from the samples using commercially available kits and the genotyping analysis for C677T MTHFR, A1298C MTHFR, A66G MTRR, A2756G MTR and 844ins68 CBS gene polymorphisms were analyzed using PCR-RFLP analysis. There was a significant difference observed in MTHFR A1298C gene polymorphism between cases and controls (P=0.008). However, there was no significant difference was observed for MTHFR C677T, MTRR A66G, MTR A2756G and CBS 844ins68 gene polymorphism. The association of MTHFR A1298C with the development of CHD in this study emphasis the role of MTHFR gene in the pathogenesis of non-syndromic CHD in Malaysian subjects

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects

Introduction: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in various populations in relation to hypertension (HTN) and type 2 diabetes mellitus (T2DM) with contradictory results.This study sought to determine the association of insertion (I)/D polymorphism of the ACE gene in hypertensive andT2DM subjects in a Malaysian population. Materials and methods: A total of 260 subjects consisting of 65 HTN, 60 T2DM, 65 T2DM with HTN and 70 controls were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of DD genotypes was performed with an insertion-specific primer. Results: The frequency for II, ID and DD genotypes of the ACE gene was 36.92%, 52.31% and 10.77% in HTN, 40.00%, 41.67% and 18.33% inT2DM, 30.77%, 53.85% and 15.38% inT2DM with HTN and 57.14%, 40.00% and 2.86% in controls, respectively. The frequency for the D allele was 36.92% in HTN, 39.17% in T2DM and 42.31% in T2DM with HTN compared to 22.86% in controls.The genotype and allele frequency of the ACE gene polymorphism differed significantly in patients when compared to controls (p < 0.05). Conclusion: The D allele of the ACE gene is associated with essential HTN and T2DM in Malaysian subjects