The FOXC2 C-512T polymorphism is associated with obesity and dyslipidemia.
The transcription factor FOXC2 has been implicated in resistance to diet-induced obesity and insulin resistance. To investigate the possible role for FOXC2 in obesity and related phenotypes, we performed two association studies for obesity using unrelated case-control materials by genotyping the FOXC2 C-512T polymorphism. In the first study (127 obese and 127 normal-weight nondiabetic subjects matched for age and sex), the C-allele showed association with obesity, odds ratio 1.74 (1.12 to 2.73; p < 0.01) for the C- vs. T-allele and 1.81 (1.04 to 3.25; p < 0.05) for the C/C and C/T vs. T/T genotype. BMI was higher in carriers of the C/C and C/T genotype in normal weight [adjusted p value (p(adj)) = 0.02] but not in obese subjects (p(adj) = 0.1). In the replication study (223 obese and 231 nonobese subjects), subjects with the C/C genotype exhibited an increased risk for obesity, odds ratio 2.01 (1.15 to 3.52; p = 0.01). Obese carriers of the C-allele had lower high-density lipoprotein-cholesterol [1.1 (0.9 to 1.3) vs. 1.2 (1.0 to 1.4) mM, p(adj) = 0.006] and increased triglyceride levels (1.95 [1.30 to 2.68] vs. 1.60 [1.10 to 2.40] mM, p(adj) = 0.02) compared with obese carriers of the T/T genotype. Our data suggest that FOXC2 is a weak but consistent candidate gene for obesity and dyslipidemia.
Carlsson
Emma
E
Department of Endocrinology, Lund University, University Hospital MAS, Wallenberglaboratory, S-205 02 Malmö, Sweden. emma.carlsson@endo.mas.lu.se
Almgren
Peter
P
Hoffstedt
Johan
J
Groop
Leif
L
Ridderstråle
Martin
M
D000005:Abdomen; D000273:Adipose Tissue; D000328:Adult; D000483:Alleles; D001823:Body Composition; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; C082078:mesenchyme fork head 1 protein