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/Hhal 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.
Xiang
K
K
Department of Endocrinology and Metabolism, Diabetes Research Laboratory, Medical Genetics Research Laboratory, Shanghai Sixth People Hospital, Shanghai 200233, China.
Zheng
T
T
Jia
W
W
Sun
D
D
Ding
W
W
Lu
J
J
Tang
J
J
D000409:Alanine / Q000235:genetics; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D003062:Codon; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D009363:Neoplasm Proteins; D013912:Threonine / Q000235:genetics; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D003062:Codon; C493404:FABP2 protein, human; C107608:FABP7 protein, human; C493405:Fabp2 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D013912:Threonine; D000409:Alanine