Sanghera D K, Saha N, Kamboh M I
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.
Atherosclerosis. 1998 Feb;136(2):217-23. doi: 10.1016/s0021-9150(97)00206-2.
Recently several but not all studies have implicated the codon 192 polymorphism in the paraoxonase 1 (PON1) gene with the risk of coronary heart disease (CHD). These findings suggest that this polymorphism is not functional but rather may be in linkage disequilibrium with a functional mutation in the PON1 or a nearby gene. In this investigation, we have evaluated the role of another common polymorphism in the PON1 gene at codon 55 with the risk of CHD in a biracial sample of Asian Indians and Chinese. We observed a significant inter-racial variability in the allelic distribution as the frequency of the less common allele, codon 55/L, was significantly higher in Indians than Chinese (0.202 versus 0.036; P < 0.0001). However, despite this inter-racial difference the codon 55 polymorphism was neither associated with CHD risk nor with plasma lipoprotein-lipids variation in both racial groups. We also used two site haplotype data (codons 55 and 192) to assess the combined contribution of the two polymorphisms to the risk of CHD. There was a strong linkage disequilibrium between the two polymorphic sites in both racial groups (P < 0.0001). While the haplotype data revealed no association with CHD in Chinese, the frequency of the BL haplotype was significantly higher (0.430 versus 0.311; P = 0.004) and the frequency of the AL haplotype was significantly lower (0.368 versus 0.483; P = 0.006) in Indian patients than controls. Since the B allele of the codon 192 polymorphism was shown to be an independent risk factor for CHD in Indians in our previous study, the positive association of the BL haplotype with CHD appears to be mediated by the B allele with no independent contribution from the codon 55 polymorphism.
最近，一些（但并非全部）研究表明，对氧磷酶1（PON1）基因中的192密码子多态性与冠心病（CHD）风险有关。这些发现表明，这种多态性并无功能，而是可能与PON1基因或附近基因中的功能性突变处于连锁不平衡状态。在本研究中，我们评估了PON1基因中另一种常见的55密码子多态性在亚洲印度人和中国人的双种族样本中与冠心病风险的关系。我们观察到等位基因分布存在显著的种族间差异，因为较不常见的等位基因（55密码子/L）在印度人中的频率显著高于中国人（0.202对0.036；P < 0.0001）。然而，尽管存在这种种族差异，但55密码子多态性在两个种族群体中均与冠心病风险或血浆脂蛋白 - 脂质变化无关。我们还使用了两位点单倍型数据（55和192密码子）来评估这两种多态性对冠心病风险的综合影响。两个种族群体中两个多态性位点之间均存在强连锁不平衡（P < 0.0001）。虽然单倍型数据显示在中国人群中与冠心病无关联，但在印度患者中，BL单倍型的频率显著更高（0.430对0.311；P = 0.004），而AL单倍型的频率显著更低（0.368对0.483；P = 0.006）。由于在我们之前的研究中已表明192密码子多态性的B等位基因是印度人患冠心病的独立危险因素，因此BL单倍型与冠心病的正相关似乎是由B等位基因介导的，55密码子多态性并无独立作用。
