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.
Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, Louisiana 70808-4124, USA. LakkaH@pbrc.edu
Hanna-Maaria
HM
Lakka
Timo A
TA
Lakka
Tuomo
T
Rankinen
Treva
T
Rice
D C
DC
Rao
Arthur S
AS
Leon
James S
JS
Skinner
Claude
C
Bouchard
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