Association of single-nucleotide polymorphisms from 17 candidate genes with baseline symptom-limited exercise test duration and decrease in duration over 20 years: the Coronary Artery Risk Development in Young Adults (CARDIA) fitness study.
BACKGROUND
It is not known whether the genes involved with endurance performance during young adulthood are also involved with changes in performance. We examined the associations of gene variants with symptom-limited exercise test duration at baseline and decrease in duration over 20 years.


RESULTS
A total of 3783 (1835 black, 1948 white) and 2335 (1035 black, 1300 white) participants from the Coronary Artery Risk Development in Young Adults study were included in the baseline and 20-year models, respectively. Two hundred seventeen single-nucleotide polymorphisms (SNPs) in black participants and 171 in white participants from 17 genes were genotyped. In blacks, 5 SNPs in the ATP1A2, HIF1A, NOS3, and PPARGC1A loci tended to be associated (P<0.05) with baseline duration in a multivariate regression model. Blacks (n=99) with at least 4 of the most-favorable genotypes at these loci had an ≈2-minute longer baseline duration than those with only 2 such genotypes (P<0.0001). In whites, the HIF1A rs1957757 and PPARGC1A rs3774909 markers tended to be associated with baseline duration, but the association of a multimarker construct of the most-favorable genotypes at both SNPs with baseline duration was not statistically significant. In whites, 4 SNPs in the AGT, AMPD1, ANG, and PPARGC1A loci tended to be associated with decrease in exercise duration over 20 years, and those with all 4 favorable genotypes (n=40) had a 0.8-minute less decline in duration compared with those with none or 1 (n=232) (P<0.0001).


CONCLUSIONS
In multimarker constructs, alleles at genes related to skeletal muscle Na(+)/K(+) transport, hypoxia, and mitochondrial metabolism are associated with symptom-limited exercise test duration over time in adults.
Sarzynski
Mark A
MA
Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Rankinen
Tuomo
T
Sternfeld
Barbara
B
Grove
Megan L
ML
Fornage
Myriam
M
Jacobs
David R
DR
Sidney
Stephen
S
Bouchard
Claude
C
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D005080:Exercise Test; D017079:Exercise Tolerance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D010809:Physical Fitness; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
D000254:Sodium-Potassium-Exchanging ATPase