stroke is the second highest cause of death in the world and the main cause of disability in people in productive ages . in indonesia , the average age of stroke patients is 58.8 years old and stroke is the leading cause of high mortality rate in people above 50 years old . statistics of heart disease and stroke2013 update reveals that number of stroke patients aged between 2045 years has increased significantly in recent years . according to world health organization , stroke is rapidly developing clinical signs of focal ( or global ) disturbance of cerebral function . the symptoms last in 24 hours or longer and may lead to death , with no apparent cause other than of vascular origin . more than 87% of stroke cases are caused by ischemia due to thrombosis or cardio embolisms . ischemic stroke is atherosclerosis - associated complication [ 35 ] which is progressive in process . it requires 3 to 4 decades or more since the period of endothelial dysfunction and carotid intimamedia thickness ( cimt ) to develop until clinical manifestations appear . a study on american children aged 1014 years old who died from motorcycle accidents showed that 50% of them have early atherosclerosis evidence . similarly , bogalusa heart study revealed that 50% of its 204 subjects aged 215 years old had fatty streak in their coronary arteries . thus , detecting atherosclerotic vascular changes in childhood helps identifying high - risk groups which is very useful for the early stroke management . cimt is a surrogate marker that reveals atherosclerosis in general and constitutes a predictor of blood vessels condition in the future . the increase of cimt has been proven to be related with the raise of ischemia stroke risk [ 1113 ] . in indonesia , cimt measurement has not yet become a routine screening procedure for atherosclerosis prevention . to date , there is no normal value data of cimt for population in indonesia . , this sign becomes very useful to be intermediate phenotype in genetic studies [ 14 , 15 ] . epidemiological data show that the increase of cimt is influenced by genetic factors , with the prediction that 30% to 40% is heritable . in 2006 , genetique de l'infarctus cerebral [ genic ] study conducted a research on genetic factors related with cimt of cerebral infraction patients . the study examined polymorphism association with vascular pathologies which incorporate inflammation , hypertension , coagulation , and lipid metabolism . the findings revealed that there was a significant relationship between cimt with monocyte chemoattractant protein-1 [ mcp-1 ] and osteopontin ( opn ) polymorphisms . mcp-1 is synthesized by various cells associated with atherosclerosis , including endothelial cells , muscle cells , fibroblasts , and macrophages . in early stages of atherogenesis , mcp-1 is primary chemokine which recruits monocytes into arterial subendothelium . mcp-1 protein and rna are highly evidenced in atherosclerotic vessels , but not in normal vessels . the mcp-1 polymorphism in the forms of snp-957 , snp-2518 , and snp-2578 causes earlier occurrence of cimt faster progression [ 12 , 1619 ] in chinese , japanese , french , and slovakian people . however , the mechanism of earlier and faster cimt development could not be identified yet . some researchers suggest that ethnic and geographic factors give different effects on genetic polymorphisms taking in mcp-1 polymorphism . thus far , there has never been a study on mcp-1 polymorphism and its contribution toward cimt conducted for indonesian population . it functions in atherosclerosis , in cell - mediated immunity , and in macrophage recruitment and activation . in early stages of atherosclerosis , opn attracts inflammatory cells , promotes the releases of proteinolytic enzymes , and stimulates smooth muscle cell proliferation . the opn promoter polymorphism is studied in several areas , such as in snp-443 and snp-66 [ 12 , 21 ] . this research attempts at explaining the effect of mcp-1 and opn promoter polymorphism on cimt changes in javanese indonesian children . subjects were 54 javanese indonesian children who were classified into two groups : case and controlled . the case group consisted of 27 children aged 1021 years whose parents had ischemic stroke historical background . the controlled group consisted of 27 javanese children aged 1021 years whose parents had no ischemic stroke history . all participants were required to complete a standardized questionnaire designed to obtain information about family history . plasma concentrations of total cholesterol , high - density lipoprotein [ hdl ] , low - density lipoprotein [ ldl ] cholesterol concentrations , triglycerides , and fasting blood glucose were measured in accordance with standardized protocols in the physiology laboratory of medical faculty , university of brawijaya malang . the research had been approved to be conducted by ethical committee , medical faculty , university of brawijaya , malang , indonesia . to measure cimt , all subjects went through carotid ultrasound process in the radiology department of saiful anwar general hospital in malang , indonesia . high resolution carotid ultrasound measurements were performed using logiq s6 ultrasound ( ge healthcare ) , with 10  mhz linier transducer . the measurement was done by scanning the far wall of common carotid arteries in 1.0  cm distal . the crest at the origin of the bifurcation was used as an anatomical mark to identify segment to be visualized . in each examination , the sonographer used three different scanning angles , namely , transversal , anterolateral , and posterolateral angles , to record the greatest cimt ( figure 1 ) [ 2224 ] . genomic dna was isolated from 1  ml blood using extraction kit ( wizard genomic dna purification kit / promega ) . mcp and opn promoters were amplified by using specific primer mcp forward 5-ccgagatgttcccagcacag-3 and mcp reverse : 5-ctgctttgcttgtgcctctt-3 . amplified dna was sequenced by employing automated sequencer ( macrogen , seoul , korea ) . data characteristics , laboratory test results and ultrasound results were tested with data normality test ( kolmogorov - smirnov ) and data homogeneity test ( levence statistics ) prior to comparison test by using independent t - test . the calculation of mutation influence on carotid artery toward cimt - increasing risks was done using the odd ratio [ or ] in a 2  2 table . each sample received the same treatment in which right and left common carotid arteries were checked , and cimt and diameter of the carotid artery were measured and calculated . result of correlation analysis on the average cimt with clinical characteristic variables is presented as in table 2 . result of correlation test carried on using pearson product moment test showed that there was no correlation between average cimt with age , height , weight , body mass index , fasting glucose , total cholesterol , hdl , and ldl , as well as triglycerides . mutations took place in base number-2138 in which adenine base had substituted to thymine base . the mutations occurred in two controlled samples ( 14.3% ) and one case sample ( 5% ) ( figure 2 ) . further mutations took place in base number-2464 in which guanine base mutated into adenine base . the calculation of mutation influence on cimt - increasing risks measured through odd ratio [ or ] using a 2  2 table appears as in table 3 . based on previous research [ 11 , 24 , 26 ] , 0.5  mm was set as the normal value of cimt for odd ratio analysis . this means that children with mutation have 1.471 times higher tendency of having cimt thickening than children without mutation . all samples were analyzed for identifying t-66 g opn polymorphism promoter , but there was no mutation found in all samples . from the research , two types of point mutation in mcp-1 gene promoters were found , that is , a-2138 t and g-2464a . either base-2138 or base-2464 was located in promoter site . the promoter determines the efficiency of rna polymerase binding and , thus , it also determines the transcription efficiency . the transcription factor is attached to the binding site in the promoter region and stimulates rna polymerase to bind with the promoter site . in japan , mcp-1a-2138 t polymorphism has been reported to be identified in myocardial infarction patients above 65 years old . it was found out that the mcp-1 a-2138 t polymorphism was significantly associated with mcp-1 serum level and incidence of myocardial infarction . in this research , mcp-1a-2138 t polymorphism was found in children from parents with ischemic stroke history and children whose parents do not have ischemic stroke history as well . the polymorphism has never been reported to be found in people with no ischemic stroke history previously . children with a-2138 t polymorphism , either from the case or the controlled group , had a thicker cimt than the normal value . the two children with a-2138 t polymorphisms had a family history of myocardial infarction disease with body mass index over 25 . ( 2006 ) informed that in japan a-2138 t polymorphism was found in patients with body mass index of more than 25  kg / m with myocardial infarction . , the polymorphism was found in the case sample of a 19-year - old girl who inherited it from the mother suffering from ischemic stroke at the age of 32 . her grandfather also suffered from ischemic stroke with hypertension , while her grandmother suffered from hypertension . her total cholesterol was 208  mg / dl and ldl cholesterol was 136  mg / dl , which indicated dyslipidemia . her average cimt was 0.60  mm , or thicker than normal average cimt [ 11 , 26 ] . results of this research reveal that children with polymorphism had thicker cimt than children without mutation . risk measured with odd ratio shows that children with mcp-1 polymorphism promoter had 1.471 times possibility to have thicker cimt than children without polymorphism . these results confirm the importance of genetic examination , especially the mcp-1 polymorphism promoter analysis in children with atherosclerosis risk factors . result of this interaction is mcp-1/ccr2 messenger system increasing activity which leads to the local recruitment of monocytes at the site of injury in the arterial wall . this , in turn , will lead to increasing atherosclerosis incidence [ 29 , 30 ] . the relation of mcp-1 promoter polymorphism with increasing cimt has been reported in several studies , in which the mcp-1 g-927c and a-2578 g polymorphisms are significantly associated with the increasing cimt in patients with ischemic stroke . the mcp-1 g-362c polymorphism in black population is associated with the increasing cimt and atherosclerosis risk . the mcp-1 g-928c polymorphism is associated with the increased cimt and the atherosclerosis risk [ 29 , 30 ] . in contrast to some other studies conducted on atherosclerosis - related conditions , this research did not result in any finding on mcp-1 a-2518 g polymorphism [ 16 , 31 ] . the difference among the above genetic polymorphism findings is likely to be due to the ethnic and geographical differences . high mcp-1 transcription rate contributes to the severity of stroke [ 32 , 33 ] . the mcp-1 transcription rate is influenced by several risk factors such as hypertension , hypercholesterolemia , smoking habit , and diabetes . in summary , two mcp-1 promoter polymorphisms were found in the research , namely , a-2138 t and g-2464a . children with polymorphism demonstrate increasing cimt and have 1.471 times higher possibility to have thicker cimt . cimt of javanese indonesian children from parents with ischemic stroke is thicker than cimt of children from healthy parents .