ABSTRACT
Objectives: To find out the association between Thrombomodulin gene polymorphism [C1418T] with coronary artery disease in population of Karachi, Pakistan
Methods: This case-control study was conducted in Tabba Heart Institute in collaboration with the National Institute of Blood Diseases, Karachi. We compared C/T dimorphism in 92 cases with 90 control subjects by allele-specific amplification. The results of PCR were confirmed by Gene sequencing. All the laboratory methods were strictly in compliance with the international standards. All variables that were either statistically significant in the univariate analyses or potentially important with respect to prevention or biologically relevant variables were included in logistic-regression analyses. Potential confounding was assessed with the use of multivariate models adjusted for participant's characteristics and other major risk factors for coronary artery disease. All reported p values are two-tailed, with statistical significance at p value <0.05
Results: The frequency of CC, C/T and TT genotype was 81 [90%], 6 [6.7%] 3 [3.3%] in controls and 67 [72.8%], 20 [21.7%] and 5 [5.4%] in cases respectively. In cases group the CT/TT genotypes were found to be significantly highly represented among the patients with coronary artery diseases when compared with control group [p-value 0.009]
Conclusion: TM C1418T polymorphism emerges as a risk marker in Coronary Artery Disease patients in the population of Karachi, Pakistan
ABSTRACT
Background and Objective: Alpha [alpha] thalassemia is a hereditary disorder and is caused by deletions or mutations in globin genes. It is present in two clinically significant forms: hemoglobin Bart hydrops fetalis [Hb Bart] syndrome and hemoglobin H [HbH] disease. It is highly prevalent in South-East Asia or Mediterranean countries. The most common deletion reported in alpha thalassemia in Pakistani population was -alpha[3.7] with a frequency of 8.3%, and the rare forms were -alpha[4.2] [0.2%] and alphaalphaalpha[anti3.7] [0.9%]. In our study, diagnosis of severe anemia cases without any alpha and beta mutations or deletions were made by using extended alpha thalassemia deletions panel. The main objective of this study was to determine the prevalence and to study the spectra of alpha thalassemia gene deletions in beta thalassemia patients with the use of an extended panel including -[SEA], --[FIL], --[MED], --[20.5], --[THAI] in addition to -alpha [3.7], -alpha [4.2] and - alphaalphaalpha[anti3.7]
Methods: The samples were collected in ethylenediaminetetraacetic acid [EDTA] vacutainers. A total of 156 samples were analyzed for alpha thalassemia mutations. This cohort included 121 samples of beta thalassemia major, nine samples of beta thalassemia minor and 26 without any evidence of beta thalassemia mutations. DNA was extracted with Qiagen extraction kit. The primers for determination of different subsets of alpha thalassemia deletions were included. PCR amplification was performed and result interpreted on agarose gel
Results: Co-inheritance of alpha thalassemia [-alpha [3.7], -alpha [4.2]] with homozygous beta thalassemia was detected in 30% cases of studied cohort [37 out of 121]. The most common found was -alpha[3.7] deletion [35/37] as single/double deletions or in combination with -alphaalphaalpha[anti3.7]. In undiagnosed cases screened for beta thalassemia major, we found Mediterranean [-alpha [MED]] deletion at specifically 875 bp on agarose gel. This is distinctive finding in case of detecting -alpha [MED] instead of any other deletion from Pakistan
Conclusion: Alpha thalassemia deletions [-alpha[3.7], -alpha[4.2]] are the common co-inherited deletions found in beta thalassemia major patients. On the basis of results, we propose an extended alpha thalassemia genetic mutation panel should be used for screening of children presenting with anemia with suspicion of haemoglobinopathy