| WHO reported that stroke was the third leading cause of death in old age and was associated with most morbidity. Carotid atherosclerosis is a common reson of ischemic stroke. China has a high prevalence of stroke. Among old people with stroke, 70% of them got carotid atherosclerosis. Carotid atherosclerosis is a marker of generalized atherosclerosis, which can prognosticate the happen of cerebrovascular diseases and other vascular incidence. It has been proved that there has some association between endothelin (ET) and the progress of atherosclerosis. Endothelin-converting enzyme (ECE) is involved in the biosynthesis of ET, which play an important role in regulating the bioactivity of ET. The genetic polymorphisms of ECE-1 C-338A and T-839G located in the ECE-1 gene promoter, the -338A allele is found to be related to coronary artery disease, and the -839G allele is found to reduce the risk of coronary artery disease. However it is unknown whether there is an association between carotid atherosclerosis and the genetic polymorphisms of ECE-1 C-338A and T-839G.Stenosis of the carotid arteries is believed to decrease cerebral blood flow. This alteration in cerebral blood flow may lead to the development of leukoaraiosis (LA).However, the association between carotid atherosclerosis and LA is still not clear.The present study includes two parts. Part one aims to investigate the association between carotid atherosclerosis and the genetic polymorphisms of ECE-1 C-338A and T-839G. Part two aims to investigate the association between carotid atherosclerosis and leukoraiosis.Part one The association between carotid atherosclerosis and the genetic polymorphisms of ECE-1 C-338A and T-839GObjectives: To investigate the association between carotid atherosclerosis and the genetic polymorphisms of ECE-1 C-338A and T-839G. Methods: A cohort of 518 Chinese Han subjects who were diagnosed as carotid atherosclerosis by Digital subtraction angiography (DSA) or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) between April 2004 and October 2008 at the Department of Neurology, Daping Hospital was enrolled. The age and sex-matched subjects who were excluded from carotid atherosclerosis by DSA or CTA or MRA during the same period were enrolled as controls.The ECE-1 C-338A and T-839G polymorphisms were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism.Results:(1) The frequencies of ECE-338CC, CA, and AA genotypes in carotid atherosclerosis patients (44.8%; 41.7%; and 13.5%) were not different from those of controls (50.8%; 39.8%; and 9.4%;χ2 = 5.884; P = 0.053). -338AA homozygote was positively related to carotid atherosclerosis (crude OR = 1.62; 95% C.I. =1.08-2.34; P = 0.02).(2) The distribution of ECE T-839G genotypes (TT , TG , GG) in carotid atherosclerosis patients (85.1%, 14.3%, 0.6%) did not significantly differ from those in controls (81.3%, 17.0%, 1.7%;χ2 = 4.674, P = 0.097). There was also no significant association between the -839G alleles genotype and carotid atherosclerosis (adjusted OR = 0.78; 95% CI = 0.56-1.13; P = 0.11).(3) After adjusted by risk factors including education, diabetes, hypertension, smoking and drinking, -338A allele carrying genotypes was significantly associated with the increased risk of carotid atherosclerosis in female(adjusted OR = 1.57; 95% CI = 1.14-2.23) and subject with age≥64 y(adjusted OR = 1.72; 95% CI = 1.23-1.41), while not in male (adjusted OR = 1.14; 95% CI = 0.58-1.63; P = NS) and subjects with age< 64 y (adjusted OR = 0.87; 95% CI = 0.61-1.24; P = NS).(4) After adjusted by risk factors including education, diabetes, hypertension, smoking and drinking, -839G allele carrying genotypes was significantly associated with the decreased risk of carotid atherosclerosis in female (adjusted OR = 0.59, 95% CI = 0.37-0.94, P = 0.03) and subject with age < 64 y (adjusted OR =0.61, 95% CI = 0.38-0.97, P = 0.04), while not in male(adjusted OR = 0.87, 95% CI = 0.54-1.37, P =NS) and subjects with age≥64 y (adjusted OR = 0.87; 95% CI = 0.61-1.24; P = NS).Conclusions: (1) The genetic polymorphisms of ECE-1 C-338A and T-839G are associated with carotid atherosclerosis(2)-338A allele carrying genotypes was associated with the increased risk of carotid atherosclerosis in female and subject with age≥64 y.(3)-839T allele carrying genotypes was associated with the decreased risk of carotid atherosclerosis in female and subject with age≥64 y.Part Two The association between carotid atherosclerosis and leukoraiosis. Objectives: To investigate the association between carotid atherosclerosis and leukoraiosis.Methods: A cohort of 243 Chinese Han subjects who were diagnosed as leukoraiosis by CT or MRI between April 2007 and March 2009 at the Department of Neurology of Daping Hospital was enrolled. The controls were selected from subjects who were exclude leukoraiosis by by CT or MRI during the same period. Carotid artery was examed by DSA or CTA or MRA. Demographic data, image date and neuropsychological test were compared between cases and controls.Results: (1) Among the 243 LA patients, 137(54.6%) patients had carotid artery atherosclerosis, 65 (26.7%) patients had carotid artery system atherosclerosis, 37 (18.5%) patients hadbasilar-vertebral atherosclerosis, 25 (10.3%) patients had atherosclerosis of both carotid artery system and basilar-vertebral artery. Among the 216 LA patients, 74(34.3%) patients had carotid artery atherosclerosis, 48(64.9%) patients had carotid artery system atherosclerosis, 22 (29.7%) patients hadbasilar-vertebral atherosclerosis, 4(5.4%) patients had atherosclerosis of both carotid artery system and basilar-vertebral artery. There was significant difference between the two groups (χ2 =6.115, P = 0.047). The carotid artery system atherosclerosis was more presented in LA patients than contrals (χ2 =24.198, P < 0.001). There was no significant difference in the distrubition of basilar-vertebral artery between LA patients than contrals (χ2 =2.010, P = 0.156), and the atherosclerosis of both carotid artery system and basilar-vertebral artery was more presented in LA patients than contrals (χ2 =12.941, P < 0.001).(2) The unilateral carotid artery system atherosclerosis was less presented in LA patients than contrals(P < 0.01). The bilateral carotid artery system atherosclerosis was more frequent in LA patients than contrals(P < 0.001). There was no significant difference in the distrubition of unilateral or bilateral atherosclerosis of basilar-vertebral artery between LA patients than contrals (χ2 = 0.342, P = 0.559), and there was no significant difference in the distribution of unilateral or bilateral atherosclerosis of both carotid artery system and basilar-vertebral artery (χ2 = 0.144, P = 0.704).(3) Most carotid atherosclerosis was light to middle extent stenosis. There was no statistic different in the extent of stenosis between LA patients and contral (X2 = 2.793,P = 0.248)and there was no significant association between the the grade of stenosis and LA.(4) There was significant difference in the character of carotid atherosclerosis plaque between LA patients and contral (X2 = 5.041,P = 0.08). After adjusted by risk factors including age, smoking, drinking, hypertension, coronary artery disease, diabetes, hyperuricemia and metabolism syndrome, lipide plague was positive related to LA patient than control (P = 0.047;Adjusted OR=1.84;95% CI = 1.47-2.98), and there was no significant difference in the distribution of mixed plaque between LA patients and control (P = 0.85;Adjusted OR = 1.97;95% CI = 0.99-2.97).Conclusions:(1) Carotid atherosclerosis increases the risk of LA.(2) The bilateral carotid artery system atherosclerosis increases the risk of LA.(3) The extent of stenosis is not associated with LA.(4) The carotid atherosclerosis plaque type is associated with LA, with lipide plaque increases the risk of LA. |
