Genetic variation in the vaspin gene affects circulating serum vaspin concentrations.
OBJECTIVE
Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine potentially linking obesity, insulin resistance and type 2 diabetes. Here, we searched for genetic determinants that could explain the variability in serum vaspin concentrations.


METHODS
First, we conducted a genome-wide association study (GWAS) for serum vaspin in the Sorbs cohort (N=826). Subsequently, 26 single-nucleotide polymorphisms (SNPs) covering genetic variation in the vaspin locus were genotyped in the Sorbs. In addition, we measured serum vaspin concentrations in 1806 samples from Augsburg/the Cooperative Health Research in the Region of Augsburg (KORA) for replication of the association signals. Finally, we conducted association analyses of vaspin SNPs with metabolic traits in the Sorbs (N=1013), KORA (N=1813) and a further cohort from Germany (Leipzig: N=1857).


RESULTS
Six SNPs mapping between serpinA1 and serpinA4, including the vaspin locus, on chromosome 14 reached P-values < or = 10(-8) in the GWAS in the Sorbs. The fine mapping of variants within the vaspin locus in the Sorbs and subsequent replication in the KORA sample revealed several SNPs significantly associated with serum vaspin concentrations reaching P-values of up to 10(-35). However, no significant association with type 2 diabetes or related traits was found in either cohort after the Bonferroni correction for multiple comparisons.


CONCLUSIONS
Our data show that the variability in serum vaspin concentrations might be explained by its genetic variants.
Department of Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
J
J
Breitfeld
A
A
Tönjes
Y
Y
Böttcher
D
D
Schleinitz
N
N
Wiele
C
C
Marzi
C
C
Brockhaus
W
W
Rathmann
C
C
Huth
H
H
Grallert
T
T
Illig
M
M
Blüher
P
P
Kovacs
M
M
Stumvoll
D000818:Animals; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005858:Germany / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D015843:Serpins / Q000097:blood*
C507339:SERPINA12 protein, human; C506516:Serpina12 protein, rat; D015843:Serpins