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- Title
Effects of Genetic Variation in the Human Retinol Binding Protein-4 Gene (RBP4) on Insulin Resistance and Fat Depot Specific mRNA Expression.
- Authors
Kovacs, Peter; Geyer, Michaela; Klöting, Nora; Graham, Tim E.; Berndt, Anin; Böttcher, Yvonne; Enigk, Beate; Tönjes, Anke; Schön, Michael R.; Kahn, Barbara B.; Blüher, Matthias; Stumvoll, Michael
- Abstract
Serum Retinol Binding Protein 4 (RBP4) is a new adipocyte-derived signal that may contribute to insulin resistance. Therefore, the RBP4 gene represents a plausible candidate gene involved in susceptibility to type 2 diabetes mellitus (T2DM) and related traits. In this study, the RBP4 was sequenced in DNA samples from 48 non-related Caucasian subjects. Five novel and 3 known single nucleotide polymorphisms (SNPs) were identified. Four SNPs, representative of their linkage disequilibrium groups were further genotyped in 504 diabetic and in 681 non-diabetic subjects. In non-diabetic subjects, 1 haplotype [C-G-T-T] was associated with significantly higher glucose infusion rate and lower waist-to-hip ratio (adjusted P<0.05). This haplotype also showed association with significantly lower mRNA levels in visceral adipose tissue in a subgroup of non-diabetic subjects with measurements of RBP4 mRNA expression in visceral and subcutaneous fat depots. In addition, three SNPs (rs3758358, rs3758539, rs10882283) were significantly associated with circulating free fatty acids (FFA) (P<0.05), which was reflected in subsequent haplotype analyses, where 1 haplotype was significantly associated with FFA and 2 other haplotypes were associated with body mass index (P<0.05). However, no association of T2DM with any of the genotyped SNPs or their haplotypes was found. In conclusion, our data indicate a minor role of RBP4 genetic variation in susceptibility to insulin 'resistance, possibly through an effect on RBP4 expression.
- Subjects
HUMAN genetic variation; VITAMIN A; CARRIER proteins; FAT cells; INSULIN resistance; MESSENGER RNA; TYPE 2 diabetes; GLUCOSE
- Publication
Diabetes, 2007, Vol 56, pA102
- ISSN
0012-1797
- Publication type
Article