Genetic Polymorphism and Stroke Subtypes in a Bangladeshi Hospital-Based Study

The association between apolipoprotein E (apoE) genetic polymorphism and stroke has not been concordant in different racial populations. We investigated the association between apoE genotypes and stroke subtypes by a case-control study in Bangladesh for the first time among south Asian countries. First-ever-stroke patients (n=227; cerebral infarction, n=147, cerebral hemorrhage, n=80) and 190 controls were recruited from a hospital in Dhaka, Bangladesh. The diagnosis of stroke was based on CT and clinical findings. Cerebral infarction was classified anatomically into cortical and penetrating region. Infarction in the cortical region was further categorized etiologically into thrombosis and embolism. Cerebral hemorrhage was considered as a whole in all analyses. ApoE genotypes were determined by restriction fragment length polymorphism. In the multivariate conditional logistic regression analysis adjusted for potential confounders both the e 3/E 4 genotype and E 4 carrier conferred an approximately 3-fold increased risk for cerebral thrombosis in the cortical artery region (OR 3.5, 95% CI 1.2 to 10.4 and OR 3.1, 95% CI 1.1 to 9.0, respectively) compared with E 3/E 3 genotype. However, when the analysis was restricted to the elderly (>60 years), e 2 carrier was associated with a risk of hemorrhagic stroke (OR 19.2, 95% CI 1.3 to 295.2). Our study suggested that both apoE E 3/E 4 genotype and E 4 carriers were risk factors for cerebral thrombosis in cortical artery region, whereas e 2 carrier was a risk factor for hemorrhagic stroke in the elderly. J Epidemiol, 2001 ; 11 : 131-138

found E 2 allele to be more common in the large-vessel atherosclerosis subtype of ischemic stroke in a German population.Of three population based studies one of which 22) detected the protective effect of E 2 in an older population, while the remaining studies 23,24) ) did not identify apo E as a risk factor for over-all stroke.These inconsistencies may be due to population heterogeneity, diversity in stroke classification, different age range, as well as small sample sizes.Of these, diversity in stroke classification renders major difficulty to interpret the results of the studies because stroke is a pathogenically and phenotypically heterogeneous disease with the role of risk factors for a stroke subtype differing from other subtypes.Most of the previous studies failed to subdivide stroke patients according to their pathogenesis.Thus, we conducted a case-control study of stroke with a distinct CT classification in a Bangladeshi hospital so that we could test the hypothesis that the apoE genetic polymorphism was related to stroke differently according to its subtypes.

Study subjects
The present design was a hospital-based case-control study of stroke.A total of 291 consecutive stroke patients were admitted to the neurology and medicine units, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh, during the period from April 1998 through February 1999.DMCH is one of the largest public general hospitals in the country providing easy access to people from all socio-economic classes.Among the stroke patients, CT findings were obtained for 262 patients.Of the CT documented patients, 4 clinically potential cerebral infarction cases failed to demonstrate any lesion on CT scan, 19 suffered recurrent stroke and 12 subjects refused to participate.227 first-ever-stroke cases were finally recruited in the present study according to the following criteria.
Cases: Stroke patients fulfilling standard World Health Organization criteria 25) for diagnosis with documented CT findings were considered as cases.
The patients were categorized into stroke subtypes on the basis of CT findings, clinical histories and examinations.Cerebral infarction (If low density area on CT image) was categorized anatomically into cortical and penetrating infarctions.Cortical infarction was further classified etiologically into (1) cortical thrombosis, if the onset of stroke had been gradual and in the absence of any source of embolism.;(2)

Participant Characteristics
As depicted in Table 1, the average age of the cases was lower than that of the controls.The ratio of males to females tended to be higher in cases than in controls.As expected, recognized risk factors, such as personal histories of hypertension, DM, and IHD in the infarction cases and only hypertension in the hemorrhage cases were more prevalent (P<0.01 for any comparisons) than in controls.Family histories of hypertension, IHD, and stroke, and higher skinfolds (P<0.01 for any comparisons) were also more frequent in cases than in controls.
Table 2 shows biochemical characteristics and BP levels according to apoE genotype in the control group.TC in E 2/ E 3 genotype (P=0.02) was lower than in E 3/E 3 genotype.However, other biochemical variables, and BP levels were not different among apoE genotypes in controls.

Allele and genotype frequencies
As shown in Table 3, there was no significant difference in as it was found only in 1 control.Since the relationship of apoE genotypes and stroke were different in the elderly and middle-aged individuals ~~, we examined the single gene effect in all ages, as well as by age group, having a cut off point at 60 years.
and Prevention through the Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.Determination of apoE genotype was performed by restriction enzyme digestion of an apoE polymerase chain reaction analyses

Table 2 .
Characteristics according to ApoE genotype in control group.
We have failed to assign 6 cortical infarctions in either of the subtypes due to confusion ; Values are row percentages.In some cases , percentages may not sum to 100% due to rounding.No significant difference was observed in the genotype distribution or allele prevalence between the control and any of the case groups.*region supplied by perforating arteries and includes internal capsule and basal ganglion .texcludes subarachnoid hermorrhage.forthose with •¸ 3/ •¸ 3 genotype.

Table 4 .
Odds ratio* (95% confidence interval) of ApoE genotypes with stroke subtypes.Diseases (9A-3) from the Ministry of Health and Welfare and another grant from the Ministry of Education, Science, Sports and Culture (No. 09470110), Japan.AHC was partly supported by Tsuji Asia Scholarship Foundation of Japan during manuscript writing.The authors wish to thank the staffs of neurology department and Dr. Ahmed Jamil Sharif of eye department of DMCH for their co-operation in data collection.We extend our special thanks to Dr. Mohammad Ali for his useful advises during manuscript writing, Dr. M.A. Rouf and Dr. Jasim Uddin and laboratory staffs of the Heart diseases Control Center, Bangladesh, for allowing us to use their laboratory during the data collection period.Japanese rural population.Stroke.2000; 31: 1299-1306.31.Zeller K, Siostrzoneck P, Lang W, et al.Different risk factor profiles in young and elderly stroke patients with special reference to cardiac disorders.J Clin Epidemiol.Wolfe B. Serum lipids after stroke.Neurology.1987; 37:507-511.36.Woo J, Lam CW, Kay R, Wong HY, Teoh R, Nocholls MG.Acute and long-term changes in serum lipids after acute stroke.Stroke.1990; 21: 1407-1411.37. Kokubo Y, Chowdhury AH, Date C, et al.Serum lipids Cardiovascular