THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots. Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54 45±9 80, male/female 1 05,body mass index (BMI)26 48±4 01] and 79 were subjects with non insulin dependent diabetes mellitus (NIDDM)(age 55 86±10 00,male/female 1 08,BMI 26 75±3 30). Design and measurements. An association study of FABP2 Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)]. Results. The geneotype and allele frequencies of FABP2 Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm 2 versus FA<75cm 2 )in NIDDM subjects (X 2 =11 460,P=0 003),with significantly increased in Thr54 carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm 2 (odd ratio for genotype was 4 62,X 2 =10 112,P=0 001;and for allele=2 36,X 2 =5 379,P=0 020).The FA in NIDDM Thr54(+)subgroup was significantly lower than that in subjects with NIDDM Thr54( )sugroup(61 19±21 51cm 2 versus 75 36±31 70cm 2 ,P=0 021). Stepwise regression analysis revealed that FABP2 Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0 003). Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2 Thr54 variant.

The impact of codon 54 variation in intestinal fatty acid binding protein gene on the pathogenesis of diabetes mellitus in Chinese

Objective To investigate whether or not the intestinal fatty acid binding protein gene (FABP2) Ala54Thr variation is related to non insulin dependent diabetes mellitus (NIDDM), obesity, dyslipidemia and glucose stimulated insulin secretion (GSIS) in Chinese.Methods The FABP2 Ala54Thr variation was detected by PCR/HhaI digestion in 231 Chinese subjects (116 with normal glucose tolerance (NGT), 54 with impaired glucose tolerance (IGT) and 61 with NIDDM). Plasma glucose, insulin and C peptide levels before and after 75 g glucose load as well as fasting lipid profile were determined.Results (1) The Ala54 and Thr54 allele frequencies in Chinese were 0.71 and 0.29 respectively; (2) The FABP2 Ala54Thr variation was neither associated with fasting and post challenged plasma glucose levels nor with NIDDM; (3) This variation was neither associated with fasting lipid profile nor with obesity; (4) The IGT subjects with genotype Thr54(+) (Thr54 homozygotes and heterozygotes) had lower fasting, 2 hour and total C peptide levels and smaller AUC representing lesser C peptide secretion after glucose challenge than those with genotype Thr54( ) (Ala54 homozygotes) (P= 0.04 , 0.03, 0.01 and 0.01 respectively). The serum insulin levels changed in the same tendency.Conclusions The glucose stimulated insulin secretion (GSIS) reserve of islet beta cells is more limited in subjects with FABP2 Thr54(+) genotype than in those with FABP2 Thr54(-) genotype. It suggests that FABP2 codon 54 variation might contribute to the insufficient insulin secretion in the development of NIDDM in Chinese.