Novel variants at KCTD10, MVK, and MMAB genes interact with dietary carbohydrates to modulate HDL-cholesterol concentrations in the Genetics of Lipid Lowering Drugs and Diet Network Study

Mireia Junyent, Laurence D. Parnell, Chao Qiang Lai, Yu Chi Lee, Caren E. Smith, Donna K. Arnett, Michael Y. Tsai, Edmond K. Kabagambe, Robert J. Straka, Michael Province, Ping An, Ingrid Borecki, José M. Ordovás

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: Several genome-wide association studies have identified novel loci (KCTD10, MVK, and MMAB) that are associated with HDL-cholesterol concentrations. Of the environmental factors that determine HDL cholesterol, high-carbohydrate diets have been shown to be associated with low concentrations. Objective: The objective was to evaluate the associations of 8 single nucleotide polymorphisms (SNPs) located within the KCTD10, MVK, and MMAB loci with lipids and their potential interactions with dietary carbohydrates. Design: KCTD10, MVK, and MMAB SNPs were genotyped in 920 subjects (441 men and 479 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Biochemical measurements were made by using standard procedures. Dietary intakes were estimated by using a validated questionnaire. Results: For the SNPs KCTD10-i5642G→C and MVK-S52NG→A, homozygotes for the major alleles (G) had lower HDL-cholesterol concentrations than did carriers of the minor alleles (P = 0.005 and P = 0.019, respectively). For the SNP 12inter-108466061A→G, homozygotes for the minor allele (G) had higher total cholesterol and LDL-cholesterol concentrations than did AG subjects (P = 0.030 and P = 0.034, respectively). Conversely, homozygotes for the major allele (G) at MMAB-3U3527G→C had higher LDL-cholesterol concentrations than did carriers of the minor allele (P = 0.034). Significant gene-diet interactions for HDL cholesterol were found (P < 0.001-0.038), in which GG subjects at SNPs KCTD10-i5642G→C and MMAB-3U3527G→C and C allele carriers at SNP KCTD10-V206VT→C had lower concentrations only if they consumed diets with a high carbohydrate content (P < 0.001-0.011). Conclusion: These findings suggest that the KCTD10 (V206VT→C and i5642G→C) and MMAB-3U3527G→C variants may contribute to the variation in HDL-cholesterol concentrations, particularly in subjects with high carbohydrate intakes.

Original languageEnglish (US)
Pages (from-to)686-694
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2009

Fingerprint Dive into the research topics of 'Novel variants at KCTD10, MVK, and MMAB genes interact with dietary carbohydrates to modulate HDL-cholesterol concentrations in the Genetics of Lipid Lowering Drugs and Diet Network Study'. Together they form a unique fingerprint.

Cite this