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Clin Nutr. 2019 Apr 4. pii: S0261-5614(19)30153-0. doi: 10.1016/j.clnu.2019.03.039. [Epub ahead of print]

Protein and fat intake interacts with the haplotype of PTPN11_rs11066325, RPH3A_rs886477, and OAS3_rs2072134 to modulate serum HDL concentrations in middle-aged people.

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Dept. of Food and Nutrition, Institue of Basic Science, Obesity/Diabetes Research Center, Hoseo University, Asan, Chungnam, 31499, South Korea.
Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam, 31499, South Korea.
Dept. of Food and Nutrition, Institue of Basic Science, Obesity/Diabetes Research Center, Hoseo University, Asan, Chungnam, 31499, South Korea. Electronic address:



Low serum HDL cholesterol (HDL-C) concentration is a risk factor for cardiovascular diseases and it is influenced by genetic and environmental factors. We hypothesized that genetic variants that decrease serum HDL-C concentrations may interact with nutrient intakes in ways that increase or decrease the risk of cardiovascular disease.


Candidate genetic variants that can lower serum HDL-C concentrations were explored by genome-wide association studies (GWAS), after adjusting for covariates, in the Ansan/Ansung cohort (n = 8842) from KoGES. The best genetic variants were selected and used to form a haplotype. According to the haplotype frequencies of SNPs, they were divided into major allele, heterozygote allele, and minor allele. The association of haplotype with serum HDL-C levels was determined using logistic regression after adjusting for confounding factors. Interaction of the haplotype with nutrient intake was also determined.


PTPN11_rs11066325, RPH3A_rs886477 and OAS3_rs2072134 were selected to modulate serum HDL-C levels from GWAS(P = 1.09E-09, 7.04E-10, and 1.27E-09, respectively). The adjusted odds ratios (ORs) for a decrease in serum HDL-C concentration in the minor-allele group of the haplotype were elevated by 1.534 fold, compared to the major-allele group of the haplotype. Furthermore, the adjusted ORs for serum LDL cholesterol and levels increased by 1.645 in the minor-alleles compared to the major-alleles of the haplotype without a significant change of serum cholesterol levels. Interestingly, the adjusted ORs for serum triglyceride were lower in the minor-alleles than in the major-alleles. The haplotype had a significant interaction with the intake of protein, fat, saturated fatty acids (SAF) and polyunsaturated fatty acids (PUFA; P < 0.05). In particular, the minor alleles of the haplotype decreased serum HDL-C levels compared to the major-alleles in the high intake of protein, fat, SFA, and PUFA, not in the low intake.


People carrying the minor-allele of haplotypes should avoid diets that are high in protein and fat, especially rich in SFA and PUFA.


Fat intake; HDL; Haplotype; Interaction; Protein intake


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