The common -866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy.
Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to type 2 diabetes (T2D). Previous studies of the role of the UCP2 promoter -866G/A single nucleotide polymorphisms (SNP) in T2D have given opposite results. We tested the distribution of the -866G/A SNP in 746 T2D patients and 327 healthy unrelated Caucasians from Italy. We also tested for an effect of the P12A variant of the peroxisomal proliferator-activated receptor-gamma 2 (PPAR gamma 2) gene on diabetes risk given by the UCP2 SNP. Compared with -866G/G carriers, a progressively reduced (P = 0.01) risk of T2D was observed in -866G/A and -866A/A subjects, with the latter showing an approximately 50% risk reduction [odd ratio (OR), 0.51; 95% confidence interval (CI), 0.3-0.8; P = 0.003]. Conversely, the -866G/G genotype was associated with increased risk (OR, 1.31; 95% CI, 1.01-1.71). Overall, the population risk attributable to the UCP2 -866G/G genotype was about 12%. After stratifying for the PPAR gamma 2 polymorphism, the increased risk conferred by the UCP2 G/G genotype was still evident among P12/P12 homozygous subjects (n = 801; OR, 1.38; 95% CI, 1.04-1.83), but seemed to disappear among the X12/A12 subjects (i.e. P12/A12 heterozygous or A12/A12 homozygous subjects; n = 137; OR, 0.87; 95% CI, 0.40-1.91). Whether this apparent difference is entirely due to the different number of carriers of the two PPAR gamma 2 genotypes is a likely possibility that deserves deeper investigation. In conclusion, in our population, the -866G/A SNP is associated with T2D. Additional studies in larger samples are needed to investigate the possibility of a concomitant effect of modifier genes such as PPAR gamma 2.
Bulotta
Angela
A
Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, 71013 San Giovanni Rotondo (FG), Italy. a.bulotta@operapadrepio.it
Ludovico
Ornella
O
Coco
Angelo
A
Di Paola
Rosa
R
Quattrone
Alessandro
A
Carella
Massimo
M
Pellegrini
Fabio
F
Prudente
Sabrina
S
Trischitta
Vincenzo
V
D000225:Adenine; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006147:Guanine; D006801:Humans; D007473:Ion Channels; D007558:Italy; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D000071246:Uncoupling Protein 2; D044465:White People
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D006147:Guanine; D000225:Adenine