Association of the 276G->T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans.
BACKGROUND
The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development.


OBJECTIVE
We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors.


METHODS
Nondiabetic subjects [n = 902; x +/- SE age: 42.5 +/- 0.53 y; body mass index (BMI; in kg/m2): 24.7 +/- 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45T-->G and 276G-->T.


RESULTS
After adjustment for age, sex, and BMI, subjects with the G allele for the SNP 276 had significantly higher concentrations of triacylglycerol and small dense LDL (sdLDL) and smaller LDL particle size than did T/T subjects. G/G subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2alpha than did T/T subjects. In the SNP 45-276 haplotype test, we also observed that subjects with the X/X haplotype had significantly higher plasma adiponectin after adjustment than did TG/TG or TG/X haplotype subjects. In the highest BMI group (BMI > or = 26), T/T subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did G/G or G/T subjects. These patterns were also seen for adiponectin in haplotype groups. However, no significant genotype effect for SNP 45T-->G was observed.


CONCLUSIONS
The 276G-->T polymorphism of the adiponectin gene modulates circulating adiponectin and IR, particularly in obese states. G allele carriers also have higher oxidative stress, higher sdLDL concentrations, and smaller LDL particle size. Therefore, the presence of the G allele in the adiponectin gene at SNP 276 could be a significant contributor to higher cardiovascular disease risk in Koreans, independent of common environmental factors.
Jang
Yangsoo
Y
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Korea.
Lee
Jong Ho
JH
Chae
Jey Sook
JS
Kim
Oh Yoen
OY
Koh
Soo Jeong
SJ
Kim
Ji Young
JY
Cho
Hongkeun
H
Lee
Jong Eun
JE
Ordovas
Jose M
JM
D052242:Adiponectin; D000328:Adult; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry; D008297:Male; D010316:Particle Size; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood / Q000737:chemistry
D052242:Adiponectin; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides