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.

A Korean-Style Balanced Diet Has a Potential Connection with Ruminococcaceae Enterotype and Reduction of Metabolic Syndrome Incidence in Korean Adults

“…We determined the number of factors based on eigenvalues >1.5, and 3 dietary factors described the distinct dietary-pattern in the participants. The orthogonal rotation procedure (varimax) was applied in the principal component analysis (PCA), and factor-loading values ≥0.40 were considered to have dominant contributions to the distinctive dietary pattern ( Table 1 ) [ 20 ]. Using clustering analysis (proc fastclus), the adults were divided into three cluster groups by calculating the distance from the assigned point after standardization of the data by proc stdize.…”

Polygenetic-Risk Scores Related to Crystallin Metabolism Are Associated with Age-Related Cataract Formation and Interact with Hyperglycemia, Hypertension, Western-Style Diet, and Na Intake

“…The 103 food items in the SQFFQ were categorized into 29 predefined food groups [ 14 , 15 ]. The food groups were used as independent variables during factor analysis conducted to find dietary patterns using the FACTOR procedure.…”

“…We determined the number of factors to retain using eigenvalues of >1.5 and 4 dietary factors describing the distinct dietary patterns of participants. The orthogonal rotation procedure (varimax) was applied during principal component analysis [ 14 ]. Factor-loading values ≥0.40 were considered to make primary contributions to distinct dietary patterns ( Supplemental Table S1 ).…”

Role of the Mitochondrial Protein Import Machinery and Protein Processing in Heart Disease

“…Previous studies indicated TOMM40 was genetically associated with cardiovascular-related traits ( 214 , 215 , 229 , 230 ). Several genome-wide association studies (GWAS) have identified that the TOMM40/APOE locus was strongly associated with low-density lipoprotein cholesterol [rs157580 ( 231 )], high-density lipoprotein cholesterol [rs2075650, ( 232 ), rs157581 ( 233 )], high-sensitivity C-reactive protein [rs2075650 ( 234 )], type 2 diabetes [rs157580 ( 231 )], or metabolic syndrome ( 235 ). Additionally, experimental evidence showed that homozygous deletion of TOMM40 in mammals was lethal, and heterozygous TOMM40 knockdown mice were found to have cardiac arrhythmia that deteriorated with age ( 236 ).…”