The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study.
OBJECTIVE
Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-alpha G-308A polymorphism and plasma CRP levels.


METHODS
Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149 women) healthy adults who underwent a 20-week standardized exercise program in the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was determined using PCR amplification followed by NcoI digestion. Plasma CRP was measured using a high-sensitivity assay.


RESULTS
Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes for the G-308A polymorphism had higher baseline CRP levels than other genotypes in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women (P = 0.032). Body mass index partly explained these associations in Blacks. The exercise program results provided further evidence for an association with the polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular exercise decreased CRP less in AA homozygotes than in other genotypes (P = 0.043).


CONCLUSIONS
The AA genotype of the TNF-alpha G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.
Lakka
Hanna-Maaria
HM
Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, Louisiana 70808-4124, USA. LakkaH@pbrc.edu
Lakka
Timo A
TA
Rankinen
Tuomo
T
Rice
Treva
T
Rao
D C
DC
Leon
Arthur S
AS
Skinner
James S
JS
Bouchard
Claude
C
D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005190:Family; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010806:Physical Education and Training; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein