Physiol. Genomics AJP: Cell Physiology
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Physiol. Genomics (March 28, 2006). doi:10.1152/physiolgenomics.00311.2005
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Submitted on December 19, 2005
Accepted on March 6, 2006

Heterogeneity of Class I insulin VNTR allele association with insulin secretion in obese children

Sophie Le Fur1, Cedric Auffray1, Franck Letourneur2, Corinne Cruaud3, Catherine Le Stunff1, and Pierre Bougneres1*

1 Hopital Saint-Vincent de Paul, Paris V University, Pediatric Endocrinology and U561 INSERM, Paris, France
2 Institut Cochin, Paris, France
3 Centre National de Sequencage - Genoscope, Evry, France

* To whom correspondence should be addressed. E-mail: pierre.bougneres{at}wanadoo.fr.

Based on the near complete linkage disequilibrium of INS VNTR with the neighbouring -23Hph1 A/T SNP, previous studies have documented the association of Class I ("short") and Class III ("long") INS VNTR with metabolic parameters, including circulating insulin. Using a new method to sequence Class I alleles, we revisited this association in 346 obese children. Class I alleles are made of several types of repeats, whose repartition determines sub-classes IC and ID. Fasting insulin was found higher in obese children with ID/ID genotypes (135 ± 12 pmol/L, n=64) than with ID/IC or IC/IC genotypes (91 ± 5 pmol/L, n=97, p=0.0005). In response to oral glucose, insulin peak and insulin to glucose area ratio were higher in ID/ID (872 ± 122 pmol/L and 109 ± 15, respectively) than in ID/IC or IC/IC patients (586 ± 42 pmol/L and 76 ± 5, p=0.02 and p=0.04). Fasting and post-glucose insulin levels were comparable in carriers of IC and of Class III alleles. Our results support that the molecular structure of the VNTR, not its overall length, is associated with variations of insulin secretion. ID/ID homozygosity appears responsible for the increased insulin levels previously attributed to the whole Class I VNTR group. It will be important to test the ramifications of this observation for Class I association with type 1 (susceptibility) and type 2 diabetes (protection).




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