Tenomodulin is associated with obesity and diabetes risk: the Finnish diabetes prevention study.
We recently showed that long-term weight reduction changes the gene expression profile of adipose tissue in overweight individuals with impaired glucose tolerance (IGT). One of the responding genes was X-chromosomal tenomodulin (TNMD), a putative angiogenesis inhibitor. Our aim was to study the associations of individual single nucleotide polymorphisms and haplotypes with adiposity, glucose metabolism, and the risk of type 2 diabetes (T2D). Seven single nucleotide polymorphisms from two different haploblocks were genotyped from 507 participants of the Finnish Diabetes Prevention Study (DPS). Sex-specific genotype effects were observed. Three markers of haploblock 1 were associated with features of adiposity in women (rs5966709, rs4828037) and men (rs11798018). Markers rs2073163 and rs1155794 from haploblock 2 were associated with 2-hour plasma glucose levels in men during the 3-year follow-up. The same two markers together with rs2073162 associated with the conversion of IGT to T2D in men. The risk of developing T2D was approximately 2-fold in individuals with genotypes associated with higher 2-hour plasma glucose levels; the hazard ratios were 2.192 (p = 0.025) for rs2073162-A, 2.191 (p = 0.027) for rs2073163-C, and 1.998 (p = 0.054) for rs1155974-T. These results suggest that TNMD polymorphisms are associated with adiposity and also with glucose metabolism and conversion from IGT to T2D in men.
Tolppanen
Anna-Maija
AM
Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. Anna-Maija.Tolppanen@uku.fi
Pulkkinen
Leena
L
Kolehmainen
Marjukka
M
Schwab
Ursula
U
Lindström
Jaana
J
Tuomilehto
Jaakko
J
Uusitupa
Matti
M
D000328:Adult; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D004032:Diet; D015444:Exercise; D005260:Female; D005387:Finland; D005838:Genotype; D018149:Glucose Intolerance / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D018579:Patient Selection; D011110:Polymorphism, Genetic; D012984:Software
D008565:Membrane Proteins; C422444:TNMD protein, human