The L513S polymorphism in medium-chain acyl-CoA synthetase 2 (MACS2) is associated with risk factors of the metabolic syndrome in a Caucasian study population.
Enzymes of the medium-chain acyl-CoA synthetase (MACS) family catalyze the ligation of medium chain fatty acids with CoA to produce medium-chain-acyl-CoA. At least four members of the MACS gene family are clustered on human chromosome 16p12. Association studies in the Japanese Suita cohort of MACS polymorphisms and various phenotypes revealed the contribution of the Leu513Ser polymorphism in MACS2 to multiple risk factors of the metabolic syndrome. Here, we investigated the association between this polymorphism and different risk factors in the Caucasian Metabolic Intervention Cohort Kiel. Seven hundred and sixteen male subjects aged 45-65 years were recruited for a standard oral glucose tolerance test and the postprandial assessment of metabolic parameters after an oral metabolic tolerance test (oMTT; 1017 kcal, 51.6% fat, 29.6% carbohydrates, 11.9% protein). The MACS2 Leu513Ser polymorphism was determined by TaqMan-Assay in 705 subjects. Postprandial triglyceride levels following oMTT [area under the curve (AUC)] were significantly higher in subjects carrying the Ser allele compared to subjects homozygous for the Leu allele (1690 +/- 100 mg x h/dL versus 1514 +/- 39 mg x h/dL, p = 0.04). Significant differences between genotype groups were also found for fasting (108 +/- 1.9 mg/dL versus 104 +/- 0.66 mg/dL, p = 0.04) and postprandial (AUC 535 +/- 11 versus 512 +/- 4.0, p = 0.02) glucose levels as well as for high-density-lipoprotein, body mass index, waist circumference, systolic and diastolic blood pressure. Carriers of the Ser allele also show an increased risk of impaired glucose metabolism (OR: 1.48, 95% confidence interval: 0.98-2.27, p = 0.07), adiposity (1.8, 1.16-2.81, p = 0.01) and hypertension (1.5, 0.99-2.17, p = 0.06). In conclusion, our results suggest an involvement of the MACS2 Leu513Ser polymorphism in the development of the metabolic syndrome in Caucasian population. Additionally, the higher triglyceride and glucose levels after an oMTT support a possible functional impact of the polymorphism in vivo.
Lindner
Inka
I
Institute for Physiology and Biochemistry of Nutrition, Federal Research Centre for Nutrition and Food, Kiel, Germany.
Rubin
Diana
D
Helwig
Ulf
U
Nitz
Inke
I
Hampe
Jochen
J
Schreiber
Stefan
S
Schrezenmeir
Jürgen
J
Döring
Frank
F
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D003066:Coenzyme A Ligases / Q000235:genetics*; D005215:Fasting; D005502:Food; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D005951:Glucose Tolerance Test; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D049629:Waist-Hip Ratio; D044465:White People
D001786:Blood Glucose; D008077:Lipoproteins, LDL; D003066:Coenzyme A Ligases; C019805:butyryl-CoA synthetase