Contribution of TNF-308A and CCL2-2518A to carotid intima-media thickness in obese mexican children and adolescents.
BACKGROUND
Although commonly used in adults to detect early atherosclerosis, the value of the carotid intima-media thickness (CIMT) in children and adolescents is not clear. This marker has an inheritable component that supports the notion of a genetic influence. Among the genes studied as candidates for atherosclerosis development are those for chemokines, cytokines, and adhesion molecules because of their participation in atheroma formation through monocyte recruitment and migration.


METHODS
We analyzed the relationship between CIMT and functional polymorphic variants in the genes for chemokines and proinflammatory cytokines associated with cardiovascular events in adults in lean and obese but otherwise healthy 6- to 19-year-old subjects.


RESULTS
In the obese group, systolic blood pressure correlated negatively (r =-0.332; p = 0.008) and the TNF-308A allele correlated positively (r = 0.262; p = 0.040) with CIMT. The mean CIMT was higher in obese individuals with the TNF-308A allele than in those with TNF-308G allele (p = 0.041). In a multiple regression model for the total population, an increase in CIMT was explained by body mass index, systolic and diastolic blood pressure, and the TNF-308A and CCL2-2518A alleles (r(2) = 0.321; p = 0.022).


CONCLUSIONS
This study contributes to the understanding of the pathophysiology of atherosclerosis and suggests that genetic markers of an increased inflammatory response and its deleterious effects are already present in obese children and adolescents.
González-Enríquez
Gracia Viviana
GV
Surgical Research Division, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jalisco, Mexico.
Rubio-Benítez
Martha Imelda
MI
García-Gallegos
Víctor
V
Portilla-de Buen
Eliseo
E
Troyo-Sanromán
Rogelio
R
Leal-Cortés
Caridad Aurea
CA
D000293:Adolescent; D000328:Adult; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002339:Carotid Arteries / Q000033:anatomy & histology*; D018932:Chemokine CCL2 / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008800:Mexico; D009765:Obesity / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D017539:Tunica Intima / Q000033:anatomy & histology*; D017540:Tunica Media / Q000033:anatomy & histology*; D055815:Young Adult
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha