The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children.
BACKGROUND
Glucokinase regulator (GCKR) plays important roles in the regulation of glucokinase (GK) activity and the metabolism of glucose and lipids. We investigated whether the association between GCKR genetic variants with serum lipids in Korean adults is replicated in children, and whether these genetic influences might be modulated by dietary monounsaturated fatty acid relative to saturated fatty acid (MUFA:SFA) ratio.


METHODS
We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements.


RESULTS
The major allele carriers of rs780094 and rs780092 in adults had significantly higher serum total cholesterol and triglycerides levels compared to noncarriers. Five variants in children, including rs780094 and rs780092, correlated similarly with high total and low-density lipoprotein (LDL) cholesterol. When the dietary MUFA:SFA ratio was dichotomized (MUFA:SFA≥1 or <1), the aggravating effects of the major allele on total cholesterol, LDL cholesterol, and triglycerides were only evident in the group in which MUFA:SFA ratio was <1. Additionally, we observed that the GCKR haplotype with a functional variant, rs1260326, influenced lower total and LDL cholesterol in children whose MUFA:SFA ratio was <1.


CONCLUSIONS
We replicated the genetic association effect of GCKR on total cholesterol in children, and found that the interaction effects between GCKR genetic variants and the dietary MUFA:SFA ratio on lipid levels, were commonly observed in Korean adults and children.
Center for Biomedical Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea. Electronic address: hyejalee@yahoo.co.kr.
Hye-Ja
HJ
Lee
Center for Biomedical Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea.
Han Byul
HB
Jang
Center for Biomedical Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea.
Hyo-Jin
HJ
Kim
Center for Biomedical Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea; Center for Genome Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea.
Younjhin
Y
Ahn
Center for Genome Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea; TheragenEtex Bio Institute Inc., Suwon, South Korea.
Kyung-Won
KW
Hong
Center for Genome Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea.
Seong Beom
SB
Cho
Department of Family Medicine, Obesity Research Institute, Seoul-Paik Hospital, Inje University, Seoul 100-032, South Korea.
Jae Heon
JH
Kang
Center for Biomedical Science, Korea National Institute of Health, Cheong Ju, Chungbuk 363-951, South Korea.
Sang Ick
SI
Park
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D004041:Dietary Fats / Q000032:analysis / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D006239:Haplotypes / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D048868:Adaptor Proteins, Signal Transducing; D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; C485100:GCKR protein, human; D008055:Lipids
Dietary monounsaturated to saturated fatty acid ratio; GCKR; Korean; Serum lipid