Impact of apolipoprotein A5 polymorphisms on insulin sensitivity and beta-cell function.
OBJECTIVE
Alternation in lipid metabolism can affect both insulin sensitivity and beta-cell function. Apolipoprotein A5 (APOA5) is an important determinant of lipid metabolism. The impact of the APOA5 gene on insulin sensitivity and beta-cell function has not been examined.


METHODS
We examined the influence of 2 amino acid polymorphisms (V150M and G182C) in the APOA5 gene on insulin sensitivity and beta-cell function in 67 glucose-tolerant white subjects. Insulin sensitivity index (ISI) and first- and second-phase insulin responses (1stIR and 2ndIR) were assessed using a hyperglycemic clamp technique.


RESULTS
We identified 59 VV and 8 VM subjects, and none had either the GC or CC genotype. Although no association was found with fasting lipid profile and plasma glucose concentrations during oral glucose tolerance test, the V150M was associated with higher 1stIR (P = 0.0010) and 2ndIR (P = 0.0016) and lower ISI (P = 0.0135). The associations of this polymorphism with 1stIR (P = 0.0081) and 2ndIR (P = 0.0087) were independent of sex, age, and body mass index, but not ISI.


CONCLUSIONS
The V150M polymorphism had an independent influence on 1stIR and 2ndIR. Although the biologic consequence of this polymorphism remains to be determined, the V150M polymorphism in the APOA5 gene is a genetic marker for beta-cell function.
Chiu
Ken C
KC
Division of Clinical Epidemiology and Preventive Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. kchiu@mednet.ucla.edu
Chiu
Yen-Feng
YF
Boyadjian
Avetis Arthur
AA
Fernando
Sandra
S
Kwan
Connie
C
Chuang
Lee-Ming
LM
D000328:Adult; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A; D005260:Female; D005838:Genotype; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A