Variants in the CRP gene as a measure of lifelong differences in average C-reactive protein levels: the Cardiovascular Risk in Young Finns Study, 1980-2001.
Genetic association studies have used variants in the C-reactive protein (CRP) gene to estimate causal effects of lifelong circulating CRP levels on disease endpoints. However, the extent to which the genetic variants are actually associated with lifelong circulating CRP levels has not been demonstrated empirically. In a population-based prospective cohort study (1980-2001) of 1,609 young Finns (768 men and 841 women), the authors genotyped five single nucleotide polymorphisms in the CRP gene (-717A/G, -286C/T/A, +1059G/C, +1444T/C, and +1846G/A) and assessed circulating CRP levels at ages 3-18 years and 24-39 years. The haplotypes from the five single nucleotide polymorphisms were associated with circulating CRP levels in childhood and adulthood, with the strongest effect being found for average CRP level across these two measures taken at two time points in the life course. In combination, the haplotype pairs accounted for 3.9%, 3.3%, and 5.0% of the variation in circulating CRP levels in childhood, in adulthood, and for the mean of CRP levels at both time points, respectively. These findings support the assumption that the above genetic variants define groups with long-term differences in circulating CRP levels.
Kivimäki
Mika
M
Department of Epidemiology and Public Health, Faculty of Biomedical Sciences, University College London, London, United Kingdom. m.kivimaki@ucl.ac.uk
Lawlor
Debbie A
DA
Smith
George Davey
GD
Eklund
Carita
C
Hurme
Mikko
M
Lehtimäki
Terho
T
Viikari
Jorma S A
JS
Raitakari
Olli T
OT
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D023381:Endpoint Determination; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D002097:C-Reactive Protein