The relationship between four single nucleotide polymorphisms in the promoter region of the osteoprotegerin gene and aortic calcification or coronary artery disease in Koreans.
OBJECTIVE
Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of the NF-kappaB ligand (RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. OPG has been proposed as a link molecule between osteoporosis and arterial calcification, but the relationship between the OPG gene and the cardiovascular system in human populations is unclear. Thus, the aim of this study was to investigate the relationship between OPG gene polymorphisms and aortic calcification or coronary artery disease in Koreans.


METHODS
Genotyping of four polymorphisms, A163G, G209A, T245G and T950C, in the promoter region of the OPG gene was performed in 251 healthy Korean women (mean age 51.3 +/- 6.9 years) and in a second study population consisting of 100 patients who underwent coronary angiography (mean age 57.0 +/- 11.9 years), by allelic discrimination using the 5' nuclease polymerase chain reaction assay. Cardiovascular risk factors and serum OPG levels were measured and aortic calcification in thoracic and abdominal aorta was examined by simple radiological methods.


RESULTS
In the first study population, the prevalence of aortic calcification increased significantly as the subjects grew older. The frequencies of mutant alleles were significantly higher in the subjects with aortic calcification compared with those without aortic calcification in G209A and T950C polymorphisms, although these significances were lost after adjustment for age. No significant relationship was found between OPG gene polymorphisms and serum OPG levels or cardiovascular risk factors. In the second study group, there were no associations between OPG promoter genotypes and aortic calcification, serum OPG levels, or coronary artery disease.


CONCLUSIONS
We observed that the four polymorphisms in the promoter region of the OPG gene were not associated with aortic calcification or coronary artery disease in Koreans. Further studies are needed to clarify this relationship.
Rhee
Eun Jung
EJ
Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oh
Ki Won
KW
Jung
Chan Hee
CH
Lee
Won Young
WY
Oh
Eun Sook
ES
Yun
Eun Joo
EJ
Baek
Ki Hyun
KH
Kang
Moo Il
MI
Kim
Sun Woo
SW
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001011:Aorta / Q000473:pathology*; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D007723:Korea; D008875:Middle Aged; D053244:Osteoprotegerin; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*; D012307:Risk Factors
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human