title: 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.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: JM-USDA-HNRCA at Tufts University, Boston, MA 02111, USA. mireia.junyent@tufts.edu
authors: Mireia
authors: M
authors: Junyent
authors: Laurence D
authors: LD
authors: Parnell
authors: Chao-Qiang
authors: CQ
authors: Lai
authors: Yu-Chi
authors: YC
authors: Lee
authors: Caren E
authors: CE
authors: Smith
authors: Donna K
authors: DK
authors: Arnett
authors: Michael Y
authors: MY
authors: Tsai
authors: Edmond K
authors: EK
authors: Kabagambe
authors: Robert J
authors: RJ
authors: Straka
authors: Michael
authors: M
authors: Province
authors: Ping
authors: P
authors: An
authors: Ingrid
authors: I
authors: Borecki
authors: José M
authors: JM
authors: Ordovás
mesh_terms: D000328:Adult; D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D004032:Diet; D004034:Diet Surveys; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D012737:Sex Factors
chemical_list: D008076:Cholesterol, HDL; D004040:Dietary Carbohydrates; C539187:KCTD10 protein, human; D024642:Potassium Channels, Voltage-Gated; D019883:Alkyl and Aryl Transferases; C019920:cob(I)alamin adenosyltransferase; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase