Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA Study.
OBJECTIVE
Epidemiological studies showing an association between the melanocortin-4-receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators.


METHODS
We analyzed this polymorphism in 7,888 adults of a population-based cross-sectional study applying regression-based statistical models.


RESULTS
Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (-1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA(1c)) (-0.09%, P = 0.040), and increased HDL-cholesterol (HDL-C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA(1c) and HDL-C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness.


CONCLUSIONS
Our representative study of well-phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient-related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.
Heid
Iris M
IM
Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany. heid@gsf.de
Vollmert
Caren
C
Kronenberg
Florian
F
Huth
Cornelia
C
Ankerst
Donna P
DP
Luchner
Andreas
A
Hinney
Anke
A
Brönner
Günter
G
Wichmann
H-E
HE
Illig
Thomas
T
Döring
Angela
A
Hebebrand
Johannes
J
D000328:Adult; D001069:Appetite Regulation / Q000235:genetics; D015992:Body Mass Index; D049628:Body Size / Q000235:genetics; D003430:Cross-Sectional Studies; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005858:Germany; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D015233:Models, Statistical; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*
D044105:Receptor, Melanocortin, Type 4