A variation in the cerebroside sulfotransferase gene is linked to exercise-modified insulin resistance and to type 2 diabetes.
OBJECTIVE
The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producing beta-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D).


METHODS
As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined.


RESULTS
A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8% versus 41.3%, P = .04). The calculated odd risk for T2D was 1.47 (1.01-2.15, P = .047). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P = .03).


CONCLUSIONS
Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.
Roeske-Nielsen
A
A
Bartholin Institute, Rigshospitalet, Ole Maaløvsvej 5, 2200 Copenhagen, Denmark. allan@roeske.dk
Buschard
K
K
Månson
J E
JE
Rastam
L
L
Lindblad
U
U
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D015444:Exercise; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013433:Sulfoglycosphingolipids / Q000097:blood; D015238:Sulfotransferases / Q000235:genetics* / Q000502:physiology; D011795:Surveys and Questionnaires; D013548:Sweden
D001786:Blood Glucose; D007328:Insulin; D013433:Sulfoglycosphingolipids; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase