Gene interactions observed with the HDL-c blood lipid, intakes of protein, sugar and biotin in relation to circulating homocysteine concentrations in a group of black South Africans

Jacomina P du Plessis; Alida Melse-Boonstra; Lizelle Zandberg; Cornelie Nienaber-Rousseau

doi:10.1016/j.ymgmr.2019.100556

Gene interactions observed with the HDL-c blood lipid, intakes of protein, sugar and biotin in relation to circulating homocysteine concentrations in a group of black South Africans

Mol Genet Metab Rep. 2019 Dec 26:22:100556. doi: 10.1016/j.ymgmr.2019.100556. eCollection 2020 Mar.

Authors

Jacomina P du Plessis¹, Alida Melse-Boonstra^{1

2}, Lizelle Zandberg¹, Cornelie Nienaber-Rousseau¹

Affiliations

¹ Centre of Excellence for Nutrition, North-West University, Private bag X6001, Nutrition, Box 594, Potchefstroom 2520, South Africa.
² Division of Human Nutrition and Health, Wageningen University & Research, P.O. Box 9101, 6700 HB Wageningen, The Netherlands.

Abstract

Background: Elevated homocysteine (Hcy) is associated with several pathologies. Gene-diet interactions related to Hcy might be used to customize dietary advice to reduce disease incidence. To explore this possibility, we investigated interactions between anthropometry, biochemical markers and diet and single-nucleotide polymorphisms (SNPs) in relation to Hcy concentrations. Five SNPs of Hcy-metabolizing enzymes were analyzed in 2010 black South Africans.

Results: Hcy was higher with each additional methylenetetrahydrofolate reductase (MTHFR) C677T minor allele copy, but was lower in methionine synthase (MTR) 2756AA homozygotes than heterozygotes. Individuals harboring cystathionine β synthase (CBS) 833 T/844ins68 had lower Hcy concentrations than others. No interactive effects were observed with any of the anthropometrical markers. MTHFR C677T and CBS T833C/844ins68 homozygote minor allele carriers presented with lower Hcy as high density lipoprotein cholesterol (HDL-c) increased. Hcy concentrations were negatively associated with dietary protein and animal protein intake in the TT and TC genotypes, but positively in the CC genotype of CBS T833C/844ins68. Hcy was markedly higher in TT homozygotes of MTHFR C677T as added sugar intake increased. In CBS T833C/844ins68 major allele carriers, biotin intake was negatively associated with Hcy; but positively in those harboring the homozygous minor allele.

Conclusions: The Hcy-SNP associations are modulated by diet and open up the possibility of invoking dietary interventions to treat hyperhomocysteinemia. Future intervention trials should further explore the observed gene-diet and gene-blood lipid interactions.

Keywords: %TCHO, percentage total carbohydrate intake; %TE, percentage of total energy; A, adenine; Ala, alanine; Asp, aspartic acid; Biotin; Blood lipid–gene interactions; C, cytosine; CBS, cystathionine β synthase; CI, confidence intervals; CV, coefficient variation; ES, effect size; G, guanine; GGT, gamma glutamyl transferase; GLM, generalized linear model; Gene–diet interactions; Gly, glycine; HDL-c, high-density lipoprotein cholesterol; HHcy, hyperhomocysteinemia; HW, Hardy Weinberg; HWE, Hardy–Weinberg equilibrium; HbA1c, glycated hemoglobin; Hcy, homocysteine; Hyperhomocysteinemia; ID, identity; ISAK, International Society for the Advancement of Kinanthropometry; Ile, isoleucine; LD, pairwise linkage-disequilibrium; LDL-c, low density lipoprotein cholesterol; MAF, minor allele frequency; MRC, Medical Research Council; MT, mutant type; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; Nutrient–gene interactions; Nutrigenetics; PA, physical activity; PCR, polymerase chain reaction; PURE, Prospective Urban and Rural Epidemiology; Precision nutrition; Protein; QFFQ, quantitative food frequency questionnaire; RFLP, restriction fragment length polymorphism; SD, standard deviations; SE, standard error; SFA, saturated fatty acids; SNP, single-nucleotide polymorphism; Sugar; T, thymine; THUSA, Transition and Health during Urbanization in South Africa; Thr, threonine; Total homocysteine; Val, valine; WT, wild type.; bp, base pairs; d, Cohen's d-value; ins, insertion.