The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit
The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit
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DOI：
10.1046/j.1469-1809.2000.6450383.x
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发表时间：
2000-09-01
影响因子：
1.9
通讯作者：
Day, INM
中科院分区：
文献类型：
--
作者：
Gu, DF;Hinks, LJ;Day, INM
长链PCR后艾德加巢式PCR以前曾用于测定CYP 2A 6 160 H等位基因，但该方法被证明是不可靠的。我们在一个包含1032名受试者（年龄范围59-74岁）的DNA库中优化了这种方法，得到了可靠的结果，产生了间接的分子证据和非常强的统计学证据，证明了迄今未被识别的共同等位基因（指定为O）与长PCR无关。编码三个等位基因（160 L，160 H和O）和关联分析的方法，最初开发用于处理ABO血型表型中隐含的无效等位基因，160 H（功能无效）对减少吸烟习惯的贡献首次被清楚地测量，不受等位基因无效对长PCR的混淆。最显著的发现（p < 0.01），与不具有160 H等位基因相比，具有160 H等位基因与开始规律吸烟的平均年龄晚3 Sears（95% CI+/-1.93岁，平均开始年龄20-21岁而不是17-18岁）;在任何时间戒烟的平均可能性为1.75倍（95%CI。1.17-2.61）。这表明，具有预测赋予50%通过CYP 2A 6途径消除尼古丁的能力的基因型的吸烟受试者戒烟的可能性几乎是两倍。
Long PCR follow ed by nested PCR has previously been used to determine CYP2A6 160H alleles; but the method proved unreliable. We have optimized this approach in a DNA bank of 1032 subjects rage range 59-74 years) to give reliable results, yielding indirect molecular evidence and very strong statistical evidence of hitherto unrecognized common alleles (designated O) recalcitrant to the long PCR. Coding three alleles (160L, 160H and O) and an approach to association analysis originally developed to deal with null alleles implicit in ABO blood group phenotyping, the contribution of 160H (functionally null) to reduced smoking habit has been clearly measured for the first time, unconfounded by alleles null to the long PCR. The most significant findings (p < 0.01) are that the possession of a 160H allele, compared with not possessing a 160H allele, is associated with a mean age of starting regular smoking 3 Sears later (95% CI+/-1.93 years, average start age 20-21 years rather than 17-18 years); and that the average likelihood of quitting smoking at any time is 1.75 fold (95% CI. 1.17-2.61) for those possessing an 160H allele compared with those who hare no 160H allele. This suggests that a smoking subject with a genotype predicted to confer 50% of the ability to eliminate nicotine via the CYP2A6 pathways has almost twice the likelihood of quitting smoking.