SNPs associated with C-reactive protein levels in a cohort of young Filipino adults. G. Curocichin1,2, T. McDade3, C. Kuzawa3, J. Borja4, L. Qin1, D. Croteau-Chonka1, A. Marvelle1, E. Lange1,5, L. Adair6, K. Mohlke1, L. Lange1 1) Department of Genetics, University of North Carolina, Chapel Hill, NC; 2) Department of Family Medicine, Moldova State Medical and Pharmaceutical University, Chisinau, Moldova; 3) Department of Anthropology, Northwestern University, Evanston, IL; 4) Office of Population Studies, University of San Carlos, Cebu City, Philippines; 5) Department of Biostatistics, University of North Carolina, Chapel Hill, NC; 6) Department of Nutrition, University of North Carolina, Chapel Hill, NC.

   C-reactive protein (CRP) is an important risk factor for cardiovascular disease. However, the effect of genetic variants on risk in young adults and in Asian populations is not clear. Studies in European midlife-to-older adult populations have identified SNPs rs1205 in the 3UTR of CRP and rs1169288 (Ile27Leu) in HNF1A as associated with serum CRP levels. We tested these SNPs for association with plasma CRP levels in young adults (21-23 years) from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) and their mothers both separately, using analysis of variance, and in a combined analysis, using general linear mixed models. A total of 1,692 young adults and 1,782 mothers (35 to 69 years) were analyzed. Median CRP levels (inter-quartile range) were 0.2 (1.0) mg/L in the young adults (range 0 to 85.9) and 0.9 (2.5) mg/L in the mothers (range 0 to 122.6). CRP levels were log-transformed and genotype was modeled as an additive effect. Log-CRP was significantly lower in the young adults than the mothers (p<0.0001). Both SNPs were strongly associated with log-CRP in the young adults and their mothers analyzed separately (all p<2x10-7) and in the combined sample (rs1205, p=6.3x10-15; rs1169288, p=2.6x10-11). In the young adults, rs1205 explains 1.7% and rs1169288 explains 1.1% of the variability in log-CRP levels. In the mothers, rs1205 explains 2.0% and rs1169288 explains 1.6% of the variability. There was no evidence for either a genotype-by-BMI or genotype-by-genotype interaction in either group. The role of hygiene remains to be analyzed. These results indicate that the CRP SNP rs1205 and the HNF1A SNP rs1169288 are associated with CRP levels in both the young adults and the mothers in this Filipino cohort, and confirm associations identified in European populations in a population of Asian descent. While CRP levels are significantly higher in the mothers versus the young adults, the effect sizes are similar in both subsets, suggesting a consistent effect of these genes on CRP levels across a wide age range. The strong evidence for association in the young adults suggests that younger populations may also be valuable in identifying genetic loci for cardiovascular disease risk factors.