N—乙酰化转移酶基因多态与肝癌遗传易感性的研究

为探讨Ｎ－乙酰化转移酶（ＮＡＴ）基因多态与肝癌遗传易感性的关系，应用ＰＣＲ、ＡＳＰＣＲ和ＲＦＬＰ，对６５例肝癌患者和１０６例健康对照进行了研究。结果表明，病例组慢型基因频率为７０．７７％，对照组为５２．８３％，两者差异显著（Ｐ＝０．００１）。ＯＲ值为２．１６，ＥＦ值为０．３８０１。提示携带慢型基因者患肝癌的危险性增加１．１６倍，由慢型基因所致的肝癌病例占人群中全部肝癌病例的３８．０１％。病例组基因型Ｆ１／Ｆ１、Ｆ１／Ｓ和Ｓ／Ｓ的频率分别为９．２３％、４０．００％和５０．７７％，对照组则分别为２２．６４％、４９．０６％和２８．３０％，两者差异显著（Ｐ＝０．００５６）。ＯＲ值分别为１．００、２．００和４．４０，存在剂量反应关系。发现４个新的慢型基因亚型，其点突变组合为３４１／５９０、５９０／８０３、２８２／３４１／５９０、２８２／３４１，将其暂命名为Ｓ９，Ｓ１０，Ｓ１１和Ｓ１２。

RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF N ACETYLTRANSFERASE AND GENETIC SUSCEPTIBILITY TO PRIMARY HEPATOCELLULAR CARCINOMA

Using PCR, ASPCR and RFLP, we studied the genotypes and genetic polymorphism of the polymorphic N acetyltransferase(pNAT) gene for 65 cases with PHC and 106 healthy controls. The pNAT gene demonstrated high polymorphism with the PIC value of 0.85 and 0.74 in the cases and controls respectively. There were two types of alleles. One is the slow type of allele transferring acetyl slowly, and the other one is the fast type transferring acetyl quickly. The frequency of the slow type allele was 70.77% in the cases, and 52.83% in the controls. the difference was statistically significant( P =0.001). OR was 2.16 and EF 0.3801, suggesting that the individual with slow type allele has a 1.16 times of the increased risk of PHC, and that the PHC cases due to the slow type allele account for 38.01% of all PHC cases in the population. The frequencies of the genotype F1/F1,F1/S and S/S were 9.23%, 40.00% and 50.77% in the cases respectively, and 22.64%, 49.06% and 28.30% in the controls respectively. The differences are statistically significant ( P =0.0056). According to the theory of the gene dosage effect, the genotypes of F1/F1, F1/S and S/S were related to various levels of exposure; their ORs of 1.00, 2.00 and 4.40 respectively simply showed a dose response relationship between the occurrence of PHC and the genotypes of pNAT. The frequencies of the phenotypes of the rapid and slow types of NAT were 49.23% and 50.77% in the cases respectively, and 71.70% and 28.30% in the controls respectively. The difference was statistically significant ( P =0.0031), OR=2.61, and EF=0.3132, suggesting that the phenotype of the slow type NAT confers 1.61 times of the increased risk of PHC, and that the PHC cases attributable to the phenotype of the slow NAT account for 31.32% of all PHC cases in the population. The observed and expected frequencies of the genotypes of pNAT were in good agreement in the control group, appearing to have achieved the Hardy Weinberg equilibrium. The results showed that the genetic polymorphism of the pNAT gene belonged to the balanced polymorphism. The new four subtypes of the slow type allele were found in the present study, their combinations of the point mutation being 341/590, 590/803, 282/341/590, and 282/341. We named them S9,S10,S11 and S12 respectively.