C-Reactive Protein Genotypes Affect Baseline, but not Exercise Training–Induced Changes, in C-Reactive Protein Levels

Abstract

Objective-The goal of this study is to determine whether C-reactive protein (CRP) gene variants affect baseline and training-induced changes in plasma CRP levels. Methods and Results-Sixty-three sedentary men and women aged 50 to 75 years old underwent baseline testing (VOmax, body composition, CRP levels). They repeated these tests after 24 weeks of exercise training while on a low-fat diet. The CRP ϩ219G/A variant significantly associated with CRP levels before and after training after accounting for the effects of demographic and biological variables. CRP Ϫ732A/G genotype was significantly related on a univariate basis to CRP levels after training. The CRP ϩ29T/A variant did not affect CRP levels before or after training. In regression analyses, the ϩ219 and Ϫ732 variants each had significant effects on CRP levels before and after training. Subjects homozygous for the common A/G Ϫ732/ϩ219 haplotype exhibited the highest CRP levels, and having the rare allele at either site was associated with significantly lower CRP levels. CRP levels decreased significantly with training (Ϫ0.38Ϯ0.18 mg/L; Pϭ0.03). However, none of the CRP variants was associated with the training-induced CRP changes. Conclusion-CRP ϩ219G/A and Ϫ732A/G genotypes and haplotypes and exercise training appear to modulate CRP levels. However, training-induced CRP reductions appear to be independent of genotype at these loci. Key Words: C-reactive protein Ⅲ genetics Ⅲ exercise training A therosclerosis, which is the main mechanism underlying most cardiovascular (CV) diseases, is now considered to be, at least partly, an inflammatory disorder. C-reactive protein (CRP) has been proposed as a marker of inflammation, 1 with lower CRP levels associated with reduced CV disease risk 2 and even slight CRP elevations associated with increased CV events. 1 Cross-sectional studies have found that CRP levels are lowest in those with the highest levels of habitual physical activity; 3 however, very few studies have assessed the impact of an exercise training intervention on CRP levels. 4 See pages 1743 and 1868Recent evidence indicates that common polymorphisms at the CRP gene locus affect CRP levels. 5,6 Four single nucleotide polymorphisms (SNPs) have been identified in the CRP gene: Ϫ732 A/G, an adenine/guanine transition in the promoter region of the CRP gene; 7 ϩ29 T/A, a thymine/adenine transversion in intron 1, 29-bp downstream (3Ј) of exon 1; ϩ1059 G/C, a silent guanine/cytosine transversion in the exon 2 coding region; 8 and ϩ219 G/A, a guanine/adenine transition in the 3Ј flanking sequence of the CRP gene, 219-bp downstream (3Ј) of exon 2. Because genetic variations affect the responses of other CV disease risk factors to exercise training, 9,10 it is possible that these CRP gene variants may interact with exercise training to differentially affect plasma CRP levels. Thus, we hypothesized that CRP levels at baseline and after 6 months of exercise training will differ among CRP genotype groups, CRP levels will decrease as a result of exercise training,...

Physiology and immunology of the cholinergic antiinflammatory pathway

“…Exercise reduces levels of TNF and other cytokines, confers protection against cardiovascular disease and type 2 diabetes, increases vagus nerve activity, and confers protection against the development of atherosclerosis (84)(85)(86)(87)(88)(89)(90). It is possible that the mechanism of these exercise effects is at least in part attributable to exercise-induced increases in cholinergic antiinflammatory pathway activity.…”

CRP and Risk of Coronary Heart Disease

“…Furthermore, proper control for concomitant factors and subgroup analyses will require a much larger sample. Thus, the study by Obisesan et al 23 should pave the way to larger intervention studies on this topic.…”

“…Obisesan et al 23 have examined some CRP gene variants at baseline and tested whether they could be related to the exercise training-induced changes in CRP levels. As previously reported, they found CRP levels to decrease with exercise training.…”

Study of C-Reactive Protein and Myocardial Infarction in the Indian Population

“…This has led to a proposition that genetic predisposition to high baseline CRP might exist due to these genetic variations and account for a significant proportion of people with a higher than average risk of coronary artery disease and MI [17][18][19][20]. There are various SNPs identified for CRP at various positions [21][22][23][24][25][26][27][28][29]. The SNPs in the promoter region might account for an increase or decrease in the overall gene expression.…”