The G-308A promoter variant of the tumor necrosis factor-alpha gene is associated with hypertension in adolescents harboring the metabolic syndrome.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) has been associated with obesity, obesity-related hypertension, and metabolic syndrome. We investigated the possible contribution of the G-308A TNF-alpha mutant to explain variables of the metabolic syndrome.


METHODS
Data and blood samples were used from the 175 adolescents that satisfied the criterion of having systolic or diastolic blood pressures (BP) more than the 80th or less than the 20th percentiles, out of a cross-sectional, population-based study of 934 high school students. Genotyping for the polymorphism was performed by polymerase chain reaction-based restriction fragment length polymorphism analysis.


RESULTS
In univariate analysis, we found that there was no difference between A allele carriers and noncarriers in most of the clinical characteristics of the metabolic syndrome such as body mass index (BMI), waist-to-hip ratio, plasma leptin levels, total cholesterol, HDL- and LDL-cholesterol, triglycerides, plasma fasting glucose, insulin, and homocysteine levels. However, we found a significantly (P = .015) higher age- and sex-adjusted systolic BP (Z score) in the A allele carriers, and A allele carriers also showed an elevated homeostasis model assessment of insulin resistance (HOMA) index with respect to noncarriers. Logistic regression analysis indicates that A allele carriers had a 2.8-fold higher probability of being hypertensive independent of BMI, waist-to-hip ratio, and HOMA index.


CONCLUSIONS
In this report we found a positive association between the G-308A TNF-alpha variant and systolic arterial BP Z score and HOMA index in adolescents harboring features of metabolic syndrome. Therefore, the A allele may predispose to hypertension and insulin resistance in youth.
Sookoian
Silvia
S
Cardiología Molecular, Instituto de Investigaciones Médicas A. Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina.
García
Silvia I
SI
Gianotti
Tomás Fernández
TF
Dieuzeide
Guillermo
G
González
Claudio D
CD
Pirola
Carlos J
CJ
D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012044:Regression Analysis; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha