The haplotype is statistically significantly higher in MI patients

The main baseline characteristics in the group of patients with MI
(n= 50) and the control group (n =50) are shown in Table (2). Age and
sex were matched between groups. Arterial hypertension, current
cigarette smoking, diabetes mellitus, hypertriacylglycerolemia,
VLDL-C, fasting blood glucose, were more prevalent in the patient
group than in the control group while HDL-C was significantly lower
in patient group than in control group (P < 0.05 for all comparisonsTable 2). We determined the genotypes of the SNPs in TSP2 (rs8089) and TSP4 (rsl866389) genes (figure 1 and 2 respectively) and observed that their distributions in the study sample were consistent with those expected for samples in Hardy-Weinberg equilibrium. Genotype distributions and alíele frequencies of the SNPs in TSP2 and TSP4 genes were not significantly different between the MI group and the control group Table (3) and table (4) respectively. Carriers of the minor alíele of the SNP in TSP2 gene (TG and GG genotypes) were present somewhat more frequently in the control group than in the patient group odds ratio (OR): 0.72; 95% confidence interval (CI)= 0.33 to 1.59 however didn't jeach a statistically significant level, whereas the proportions of minor alíele carriers of the SNPs in THBS4 was not substantially different between the study groups (TSP4 genotype: OR: 1.49; 95% CI= 0.67 to 3.29). There was no statistically significant difference in MI patients carriers of minor alíele of TSP2 versus carriers of major alíele (GT and GG versus TT) regarding all the measured conventional risk factors the total cholesterol was statistically significant higher {P=Q.O2) in 174 . carriers of minor alíele (C) of TSP4 versus carriers of major alíele (GC and CC versus GG) while no statistically significant difference was observed regarding all the other measured conventional risk factors.The frequency of TT/GC haplotype is statistically significantly higher in MI patients (24%) than in controls (6%) F value=0.0226 while the distribution of the other haplotypes showed no statistically significant difference between the MI and control group (table 5). Table (1): TaqMan probes used for genotyping ofthe thrombospondin gene (THBS) single nucleotide polymorphisms (SNPs)DISCUSSIONIn the case-control sample examined here , no association of theSNP in TSP2 with MI was found, while a high (7%) frequency of theminor alíele (G) in the control group (34%) than in the patient group(27%) was existed, although it didn't reach a significant level (OR-0.718, 95%CI=0.3921 to 1.3149,P=1.156) . Previous study done byAshokKumar et al. (2011) on South Indian population found noassociation of the polymorphism (3949 T-^G) in TSP-2 gene with MIThe same result was reported by Peyvandi et a/.(2003) on Italianspopulation, 1539 MI patients and 1539 controls, revealed that there is178 ___^_^____ ^no association between Ml and TSP-2 gene polymorphism (3949T^G).In contrary, the Dutch study performed by Boekholdt et al. (2002)showed that the frequency of the minor alíele (G) in the control group(25%) is higher than in ihe MI group (20%) but the Homozygosity forthe TSP-2 variant alíele was significantly associated with a reducedrisk of premature MI compared with wild-type individuals.Moreover, "the GeneQuest study", one of the largest genetic studies ofits kind, researchers, by using 'highthroughput' microarraygenotyping to sift through 62 genes from 352 people with MI and 418individuals without, discovered three genetic variants in the TSPprotein family that might explain why some families are prone topremature heart disease. Of them, A variant in the 3' untranslatedregion of thrombospondin-2 (change of thymidine to guanine) seemedto have a protective effect against MI individuals homozygous for thevariant (Topol et al., 2001)However, although a meta-analysis of available data till 2008 done byKoch et al. (2008) showed that the carriers of the minor alíele of thepolymorphism in the TSP-2 gene (GG and TG genotypes) amongGerman population had a mildly statistically significant higher risk ofMI than the homozygous carriers of the major alíele (TT genotype)adjusted odds ratio (OR) 1.19; 95% confidence interval (CI), 1.02 to1.39. Combined examination of the results of the different studiesinvolved in the meta-analysis strongly suggested that the SNP in TSP2was not associated with the disease.The discrepancy of the results could be explained by differences insample collection between our study and the GeneQuest study. One ofthe important differences between the studies is that unlikeGeneQuest, our control group was matched to the cases by gender andethnicity to avoid genetic' admixture. Another difference is thatpatients with MI in GeneQuest were enrolled on average 9 to 10 yearsafter their first MI; they represent a group of survivors of MI.Therefore, it is possible that the observed association is not with thedevelopment of MI, but rather with survival after MI. Moreover,inclusion criteria in GeneQuest required that at least one sibling of theproband also fulfilled the criteria for premature CAD, a requirement,not used in our study.In our study, we observed that there is no association of the minoralíele (C) of SNP in TSP4 gene (rsl866389) with MI (OR: 1.0612,^ - 179(DaíiCia I (ßadran et aŒ95% confidence interval (CI) = 0.3093 to 3.6407,/;= 1.00). Thus, thereis no increased risk of MI in subjects that have the minor alíele (C).Lack of associations between TSP4 polymorphism and MI wasreported in several studies. A meta-analysis on German populationrevealed no association of the polymorphism in TSP4 gene with MI(adjusted OR: 0.99; 95% CI= 0.85 to .6,p = 0.81). Another studiesdone on the American population revealed no association between thepolymorphism and MI (Asselbergs et al., 2006 ;Wessel et al., 2004;Morgan et al., 2007) , the same was reported by Cui et al. 2006 onCanadian population and Yamada et al, 2002 on Japanese populationand our study is also consistent with Zhou et al. (2004) on Chinesepopulation. In contrary, the GeneQuest study discovered three geneticvariants in the TSP protein family that might explain why somefamilies are prone to premature heart disease. Of them, the TSP-4A387P variant showed the strongest association (OR for MI =1.89, F=0.002) for individuals carrying the C alíele (Topol et al., 2001),Among the possible reasons for these differences were small samplesizes in some instances, lack of correction for multiple hypothesistesting, application of different risk models, different age ranges ofstudy participants, assessment of related but not identical diseasephenotypes, different definitions and procedures for establishment ofcase status, and different recruitment strategies for control individuals,in addition to the ethnic factors.In addition, it was possible that the TSP-4 variant conferred amodestly increased or reduced risk that might be added to, amplifiedor even overcome by other acquired environmental and/or additionalgenetic factors. Furthermore, the study subjects were not recruitedprospectively; therefore, a survival bias could not be excluded.Moreover, the controls were composed of clinically asymptomaticsubjects with normal ECGs and were not presumed to have CAD.Some of them might have also had asymptomatic, but significant,CAD or they might have developed CAD at a later stage.However, TTGC haplotype is statistically significantly higher in MIpatients (24%) than in controls (6%) F value=0.0226 which mayindicates that homozygotes for the major alíele of TSP2 gene (TT) andHétérozygotes (GC) for TSP4 gene have a high risk for developingMI.CONCLUSION :Our data suggests that although association analysiswith MI did not reach significance, an at-risk haplotype of common180Ii^^S OT 'B{

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