CYP11B2 gene polymorphism among coronary heart disease patients and blood donors in Malaysia

Various previous studies have reported the implication of CYP11B2 gene polymorphism in the pathophysiology of cardiovascular diseases. In particular, the -344T/C polymorphism, which is located at a putative binding site for the steroidogenic transcription factor (SF-1) has been associated with essential hypertension, left ventricular dilation and coronary heart disease. In the present study, we aim to determine the allele and genotype frequencies of the CYP11B2 gene in patients with clinical manifestation of coronary heart disease and confirmed by angiography and blood donors and to calculate the association of the gene polymorphism with CHD. A total of 79 DNA from patients with coronary heart disease admitted to the National Heart Institute and 84 healthy blood donors have been genotyped using polymerase chain reaction technique followed by restriction enzyme digestion (RFLP). Results of the study demonstrated that out of 79 for the patients, 40 were homozygous T, 10 were homozygous C and 29 were heterozygous TC. The frequencies of genotype TT, CC and TC for patients were 0.5, 0.13 and 0.36 respectively. The frequencies of allele T and C in patients were 0.68 and 0.31 respectively. While for the blood donors, 40 subjects were of homozygous T, 7 were homozygous C and 37 were heterozygous TC. The genotype frequencies for the TT, CC and TC were 0.47, 0.08 and 0.44 respectively. The frequency of the allele T was 0.69 and allele C was 0.3. Chi-Square analysis showed that there was no significant difference in the genotype and C allele frequencies between the CHD patients and the blood donors. Our study suggests that there is lack of association between -344T/C polymorphism of CYP11B2 gene and coronary heart disease.

Association of the tumor necrosis factor alpha gene polymorphism with susceptibility and clinical-immunological findings of systemic lupus erythematosus.

The etiology of systemic lupus erythematosus (SLE) is unknown but genetic factors seem to play a role in the disease pathogenesis. The tumor necrosis factor alpha (TNFa) gene, encoded at the TNF locus in the MHC class III region, is now known to be an important candidate gene in SLE, due to the proinflammatory activities of the TNFa. The objectives of this study were to examine the role of the TNFa polymorphism for the susceptibility of Malaysian Chinese lupus patients to SLE and to determine its association with organ involvement. The allelic frequencies of the TNFa polymorphic variant (TNF2) of seventy lupus patients were determined during follow-up at the Medical Clinic of the National University Hospital Malaysia by PCR-RFLP technique. Sixty-four females and 6 males with a mean age of 33+/-12 years were included. Clinical data were obtained from case records. Autoantibody levels were measured by ELISA. Fifty-nine ethnically-matched blood donors were used as controls. The allelic frequency of the TNF2 variant was found to be significantly increased in the patients compared to the controls (52.8% vs 33.8%). SLE patients with the polymorphic TNF2 variant were found to be at increased risk of central nervous system involvement (p = 0.004, RR = 2.59) and to have an increased frequency of anti-La antibodies (p = 0.03). In view of these findings we suggest that TNF2 variant is playing a role in conferring susceptibility to SLE and in the disease pathogenesis.

The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus.

The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.

Seroprevalence of Sarcoptes scabiei var canis antibodies among aborigines in peninsular Malaysia.

The Aborigines or Orang Asli in Peninsular Malaysia who are still seminomadic are known to have a close association with dogs. In this study, enzyme-linked immunosorbent assay (ELISA) was used to detect anti-Sarcoptes scabiei var canis antibodies in this community as a measure of exposure to the mite. Out of 312 Orang Asli tested, 24.7% were positive for polyvalent anti-Sarcoptes antibodies. No significant difference was found between the positive rates in males (26.1%) and females (23.6%). Only 1.9% were positive for IgA and none was positive for IgE anti-Sarcoptes antibodies. Since there were very few patients with clinical manifestation of scabies, there is a possibility that continuous exposure to the dogs mite confers cross-protective immunity in the community against human scabies.

Seroprevalence of Toxocara canis antibodies among Orang Asli (aborigines) in Peninsular Malaysia.

An enzyme-linked immunosorbent assay using excretory-secretory antigens of the second stage larvae maintained in vitro was used to determine the seroprevalence of Toxocara antibodies in Orang Asli (aborigines) of Peninsular Malaysia. The mean + 3 SD optical density of 30 healthy subjects was used as the cut-off point. Overall prevalence was found to be 31.9%. No significant relationship was found between positive rates with sex and age groups, though children between 0 to 9 years recorded the highest positive rates. Eosinophil counts were found to be closely related to the proportion of positivity to toxocaral infection and mean optical densities. There was some degree of cross-reaction with Trichuris trichuria positive sera.