A minor allele of the haplotype located in the 19q13 loci is associated with a decreased risk of hyper-LDL-cholesterolemia, and a balanced diet and high protein intake can reduce the risk

Abstract

Background: Although the human chromosome 19q13 loci are reported to be associated with hyper-LDL-cholesterolemia, the haplotype of single nucleotide polymorphism (SNP) has not been studied. Therefore, the association of the haplotype in 19q13 loci with hyper-LDL-cholesterolemia was determined and their interactions with lifestyles and nutrient intakes were evaluated in 28,445 Koreans aged > 40 years.

Methods: SNPs were selected from 19q13 loci that had an association with hyper-LDL-cholesterolemia with the adjustment of confounders (age, gender, area of residence, and body mass index). Haplotype was constructed from the selected SNPs. An adjusted odds ratio of the haplotype for hyper-LDL-cholesterolemia and the interaction between haplotype and lifestyles was analyzed after adjusting for covariates.

Results: Hyper-LDL-cholesterolemia had an association with apolipoprotein E (APOE)_ rs7259620, translocase of outer mitochondrial membrane 40(TOMM40)_rs157581, poliovirus receptor-related 2(PVRL2)_rs403155, exocyst complex component 3-like 2(EXOC3L2)_ rs10406604 and CD3e molecule-associated protein (CD3EAP)_rs3212986 in 19q13. The haplotype of these SNPs had a negative association with hyper-total-cholesterolemia and hyper-LDL-cholesterolemia by 0.669 and 0.684 times, respectively, after adjusting for covariates. The incidence of cardiovascular diseases, especially myocardial infarction, had a negative association with the minor alleles. The balanced diet pattern (BD) and protein intake had a significant interaction with the haplotype: the major-allele of the haplotype exhibited a positive association with hyper-LDL-cholesterolemia, compared to the minor allele, only when combined with a high intake of BD. The participants with the minor allele exhibited a lower hyper-LDL-cholesterolemia risk compared to those with the major allele only with high protein intake.

Conclusion: The minor allele of haplotype located in 19q13 loci protected against hyper-LDL-cholesterolemia, especially with BD and high protein intake. The minor allele also had a negative association with myocardial infarction events.

Keywords: 19q13 loci; Apolipoprotein E; Dyslipidemia; Low-density lipoprotein; Protein.

Fig. 1

Haploview in the 19q13 loci. Haploview of the 19q13 loci. Each value in the colored rectangle represents the D’ between a pair of SNPs and the range of the value 0–100. The lighter color in the haploview indicates a lower correlation between the adjacent SNPs in the haplotype. The numbers in the triangles represent the correlation coefficient between the adjacent SNPs

Fig. 2

Serum LDL concentrations of participants with major, heterozygotes and minor alleles of haplotype with SNPs in the 19q13 loci. A: Balanced diet pattern (cutoff value: 75th percentiles); B: Protein intake (cutoff value: 13 energy percent (En%). Non-risk, heterozygotes, and risk alleles of each SNP were scored 0, 1, and 2, respectively, and the scores of each SNP in the haplotype were combined. The scores were divided into 3 categories (Major, Heterozygote, and Minor groups) by 0, 1–2, and 3–4, respectively. ^a,b,c Means without a common letter differ among the different allele groups by Bonferroni test at P < 0.05 in the low intake category. ^{a’,b’,c’} Means without a common letter differ among the different allele groups by Bonferroni test at P < 0.05 in the high intake category