A SNP haplotype of the forkhead transcription factor FOXO1A gene may have a protective effect against type 2 diabetes in German Caucasians.
OBJECTIVE
The human protein encoded by the FOXO1A gene functions as a transcription factor of insulin signaling key genes. In this study we investigated the role of genetic variation in the FOXO1A gene in susceptibility to type 2 diabetes (T2D) and relevant metabolic traits.


METHODS
We genotyped six haplotype tagging single nucleotide polymorphisms (SNPs) for association analyses in German Caucasians (593 patients with T2D and 760 non-diabetics, who included 594 normoglycemics and 166 individuals with impaired glucose tolerance).


RESULTS
In a case control study involving all type 2 diabetics and healthy controls with normal glucose tolerance, none of the FOXO1A SNPs showed any association with T2D. However, the frequency of the [C-C-G-A-A-A] haplotype comprising six FOXO1A SNPs was 36.5% in normoglycemic non-diabetic controls compared to 31.0% in type 2 diabetic patients (P=0.004). Consistent with this, the same haplotype was significantly associated with lower fasting plasma insulin, BMI, HbA(1C), free fatty acids and % body fat in all non-diabetic subjects (all adjusted P<0.05).


CONCLUSIONS
In conclusion, our study suggests a protective effect of FOXO1A haplotype [C-C-G-A-A-A] on T2D development and relevant intermediate phenotypes which predispose for T2D.
Böttcher
Y
Y
Medical Department III, University of Leipzig, 04103 Leipzig, Germany.
Tönjes
A
A
Enigk
B
B
Scholz
G H
GH
Blüher
M
M
Stumvoll
M
M
Kovacs
P
P
D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000517:prevention & control*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006442:Glycated Hemoglobin; C085126:FOXO1 protein, human