Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase [MTHFR] C677T, A1298C; methionine synthase [MS] A2756G; cystathionine-beta-synthase [CBS] 844ins68, G919A polymorphisms with premature acute myocardial infarction [AMI] in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients [age <45 years] and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23 +/- 17.2 and 23 +/- 13.4 micro mol/l, respectively which are higher than the upper normal limit of this biomarker [15micro mol/l]. MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine [p value <0.05], while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population

Antipsychotic treatment and weight gain: does risperidone behave differently in Pakistani psychiatric patients?

Studies from the Western world have shown that antipsychotic medications in psychiatric patients result in weight gain and other metabolic diseases. This study was undertaken to investigate whether any one of the five most commonly prescribed antipsychotics, [risperidone, olanzepine, trifluoperazine, quetiapine and haloperidol] could behave differently in terms of causing weight gain among patients attending the psychiatric outpatient clinics in a tertiary care hospital in Karachi, Pakistan. For this retrospective cohort study, data were collected from outpatient records of the Aga Khan University Hospital, from 2003 to 2007. Demographic and clinical data were analysed. Repeated measures ANOVA, using a linear mixed model approach was used to assess weight gain over time due to the use of antipsychotic medications. A total of 124 subject records [68 males and 56 females] were evaluated. One-way ANOVA revealed that the groups being prescribed with antipsychotics were comparable with respect to age, duration of treatment and weight measurements. Frequencies were calculated which showed that weight increases significantly over time with respect to the prescribed antipsychotic medications, except for risperidone. Repeated measures ANOVA using the linear mixed model approach showed that the serial weight measurements were significantly different across the follow up times [p<0.05]. Four of the commonly prescribed antipsychotic drugs do result in an increase in weight; however risperidone has no such effect, making it an option in treating psychiatric disorders without worrying for any gain in weight. In view of the increased prevalence of obesity and other metabolic diseases, measures should be taken towards careful prescription of antipsychotic medications

Gastrointestinal abnormalities in vitamin B[12] deficient patients with megaloblastic anemia

In a retrospective cohort study, hospital records of 220 patients [119 males and 101 females, age 1 year-80 years] with megaloblastic anemia were examined to find out any relationship of gastrointestinal abnormalities with vitamin B[12] and folate deficiencies in these patients. Forty three percent of the patients were folate-deficient [serum folate levels

comparison of treatments offered to patients with nonalcoholic steatohepatitis

To compare various treatment options provided to patients with Nonalcoholic Steatohepatitis [NASH] and assess improvement in liver status via reduction in serum Alanine Aminotransferase [ALT] levels. Study Design: Retrospective cohort study. The Aga Khan University Hospital, Karachi, from April 2000 to April 2007. Methodology: All available records of patients aged between 20-70 years, fatty liver on ultrasound, elevated serum ALT and having at least one follow-up, after a baseline visit were included. The patients had variable number of follow-ups and a maximum of 3 follow-ups were considered. Information was collected on demographic and clinical characteristics of the subjects. The treatment options were categorized as weight reduction alone, with statins, and with other medications. Serum ALT level was the main outcome measured in IU/l. Repeated-measures ANOVA, using a mixed model approach was performed with treatment options as between subject factor, and follow-up as within subject factor and p-value < 0.05 was considered significant. Sixty-nine records of subjects, consisting of 50 males and 19 females were selected. The mean [ +/- SD] age was 40 +/- 12 years. Thirty-one subjects [45%] were advised weight reduction only, and experienced a 72% reduction in serum ALT levels, over the mean follow-up time of 9 +/- 3 months. Twelve subjects [17%] received statins along with weight reducing advice, and experienced a 56% reduction in mean ALT over the mean follow-up of 11 +/- 7 months. Twenty-six subjects [38%] received other medications along with advice for weight reduction and experienced a 73% reduction in serum ALT levels over the mean time of 10 +/- 4 months. The mean ALT declined at follow-up times, irrespective of the prescribed treatment, and that the decline with time was different for males and females. Serum ALT levels among patients with NASH decreased with time, regardless of the provided treatment, and the decrease was different for males and females

Human paraoxonase and HDL-cholesterol in Pakistani patients with acute myocardial infarction and normal healthy adults

Human serum paraoxonase is a high density lipoprotein [HDL]-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction [AMI] compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol [serum levels<40mg/dl] compared to the value in those with normal levels of HDL-cholesterol [P=0.04]. In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol [Pearson's r=0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls]. Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population