on December 12, 2002
Published online before print December 12, 2002, doi: 10.1161/01.ATV.0000051702.38086.C1
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Submitted on November 8, 2002
Accepted on November 22, 2002
Extensive Association Analysis Between Polymorphisms of PON Gene Cluster With Coronary Heart Disease in Chinese Han Population
Xiaoling Wang ;
From the Division of Population Genetics (X.W., J.H., Q.Y., S.S., J.Z., D.G.), Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; National Human Genome Center at Beijing (X.W., Y.S., B.Q., D.G.); Sino-German Molecular Medicine Laboratory (R.H.), Cardiovascular Institute, Fu Wai Hospital; and Peking Union Hospital (Z.F.), Beijing, China.
* To whom correspondence should be addressed. E-mail: gudf{at}yahoo.com.
Objective—An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population.
Methods and Results—Thirty polymorphisms of PON1, PON2, and PON3 gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients. Twelve polymorphisms were additionally investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele, and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P=0.0054 and P=0.0002). Haplotype analyses for various polymorphism combinations additionally confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher, whereas only the frequencies of haplotypes containing 160G allele were significantly lower in cases than in controls in various polymorphism combinations.
Conclusions—This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population and warrants additional study to elucidate the biological mechanism.
Key words: coronary heart disease • genetics • paraoxonase • linkage disequilibrium • LDL oxidation
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