Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects.
OBJECTIVE
Neuropeptide Y (NPY) plays a central in energy homeostasis and potentially in the development of obesity-related comorbidities, like type II diabetes. As the PreproNPY Leu7Pro polymorphism probably changes the intracellular processing of the synthesized preproNPY peptide, we assessed the hypothesis that PreproNPY Leu7Pro polymorphism is a risk factor for type II diabetes, impaired glucose tolerance and hypertension.


METHODS
Blood pressure recordings and oral glucose tolerance test were performed in the hypertensive (n=515) and control cohorts (n=525) of our well-defined Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study. The prevalence of type II diabetes was 9% (n=93). The genotypes, insulin and glucose metabolism indexes and plasma ghrelin of the subjects were determined.


RESULTS
Pro7 allele frequencies were 5.9, 5.3 and 11.3% in the total cohort, in subjects without and with type II diabetes, respectively. The PreproNPY Pro7 carrier status was a significant risk factor for type II diabetes, and the effect remained significant after adjustment for age, sex, waist circumference and study group (odds ratio=3.02, confidence interval: 1.67-5.44 and P<0.001). Pro7 carriers were more insulin resistant and showed lower ghrelin levels compared to non-carriers.


CONCLUSIONS
The PreproNPY Pro7 allele is associated with an increased risk for type II diabetes. The risk seems to be associated with a higher insulin resistance among Pro7 carriers whereas low ghrelin concentrations in Pro7 carriers are possibly a consequence of high insulin levels.
Ukkola
O
O
Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland. olavi.ukkola@oulu.fi
Kesäniemi
Y A
YA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D054439:Ghrelin / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics*; D036361:Peptide Hormones / Q000097:blood; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D012307:Risk Factors
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011498:Protein Precursors; C042084:preproneuropeptide Y; D011392:Proline; D007930:Leucine