Frequency distribution of the single-nucleotide -108C/T polymorphism at the promoter region of the PON1 gene in Asian In
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ORIGINAL ARTICLE
Frequency distribution of the single-nucleotide -108C/T polymorphism at the promoter region of the PON1 gene in Asian Indians and its relationship with coronary artery disease Imteyaz Ahmad & Rajiv Narang & Anand Venkatraman & Nibhriti Das
Received: 17 September 2010 / Accepted: 21 January 2011 / Published online: 7 February 2011 # Springer-Verlag 2011
Abstract A single-nucleotide promoter region polymorphism (-108C/T) of the paraoxonase (PON1) gene had been suggested to influence an individual's susceptibility to coronary artery disease (CAD). No data is available on this polymorphism from India. One hundred seventy-eight healthy individuals and 204 angiographically proven CAD patients were recruited to get baseline data on the frequency distribution of the -108C/T polymorphism in normal people of Asian Indian ethnicity and its relation with the risk of CAD. Polymerase chain reaction followed by restriction fragment length analysis was used as the method for genotyping. Blood samples were used for DNA isolation. In the normal subjects, the genotypes were distributed as CT (43.26%)>CC (30.34%), >TT (26.4%). The allele frequency of the C allele was 0.52, and that of the T allele was 0.48. The patients showed a similar pattern, but the TT genotype was about two times more frequent in the controls than in patients. Odds ratios for developing CAD for individuals with CT, TT, and CT + TT genotypes were 0.89 (0.50–1.59), 0.56 (0.27–1.08), and 0.76 (0.44–1.29), respectively (at 95% confidence
I. Ahmad : A. Venkatraman : N. Das (*) Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India e-mail: [email protected] N. Das e-mail: [email protected] R. Narang Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
interval), when compared to CC homozygous people (ageand sex-adjusted, p=0.114, all genotypes compared). This suggested a trend for the T allele as protective against CAD. This first report on the frequency distribution of the -108C/T polymorphism in people of Asian Indian ethnicity suggests that the normal distribution is similar to that observed for the Chinese, Japanese, and Latino people, but the disease association is unique. The TT genotype and the T allele which are widely found associated with the risk of CAD showed a protective trend in this study. Keywords PON1-108C/T . Coronary artery disease . Asian Indians
Introduction Serum paraoxonase (PON, aryldialkylphosphatase) is a glycoprotein which circulates in the dense HDL subfraction that also contains Apo-E and Apo-J (Bergmeier et al. 2004). Human serum paraoxonase (E.C.3.1.1.2) catalyzes the hydrolysis of the organophosphate paraoxon to the nontoxic products, p-nitrophenol and diethylphosphoric acid (Aldridge 1953a, b; Erdos and Boggs 1961). Much of the early interest in this enzyme was related to its role in organophosphate pesticide toxicity. Paraoxonase has also been recognized as a key contributor to the anti-LDL oxidant functions of HDL (Garner e
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