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.
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.
Junyent
Mireia
M
JM-USDA-HNRCA at Tufts University, Boston, MA 02111, USA. mireia.junyent@tufts.edu
Parnell
Laurence D
LD
Lai
Chao-Qiang
CQ
Lee
Yu-Chi
YC
Smith
Caren E
CE
Arnett
Donna K
DK
Tsai
Michael Y
MY
Kabagambe
Edmond K
EK
Straka
Robert J
RJ
Province
Michael
M
An
Ping
P
Borecki
Ingrid
I
Ordovás
José M
JM
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
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