| Objective:To investigate the distribution of NAT2, CYP2E1RsaI, GST genes polymorphisms in healthy population and pulmonary tuberculosis cases of Xinjiang province. In order to provide basic data for the further study on gene polymorphisms and the correlation of human chronic diseases.Moreover, provide data support for the future to explore gene polymorphisms and drug-drug interaction mechanism and realization of the individualized treatment. Method:The study population was obtained from three region of Xinjiang province.We conducted a cross-sectional epidemiological study including 1675 patients. The genotypes of NAT2[481 (rs1799929),590 (rs1799930) and 857 (rs1799931)], CYP2E1RsaI, GST were detected by PCR-LDR technique. Articles about NAT2, CYP2E1RsaI, GST polymorphisms published from January,2003 to December, 2013 in China were searched. Results:1) Our study in Xinjiang province NAT2 genotype of three SNPS loci in tuberculosis patients 481 (rsl799929),590 (rs1799930) and 857 (rs1799931) are was found as a major genotype in wild type, the frequency were 68.4%, 56.9% and 79.4% respectively; NAT2 metabolic phenotype in the middle type acetylation was the highest (47.7%), followed by slow acetylated type (30.6%); CYP2E1RsaI genotype frequency is was found as a major genotype in wild type (76.7%), followed by heterogeneous type (21.1%). The frequency of GSTM1 and GSTT1 homozygous null genotypes were 53.9% and 29.3%.GSTM1 and GSTT1 combined homozygous null genotypes in tuberculosis patients were 16.7%.2) Population distribution in 481 (rs1799929) SNPS loci and acetylated metabolism of NAT2 phenotype found a statistical significance between different ethnic groups (P<0.05), however, found no statistical differences between different gender, age, smoking, drinking (P>0.05); In 590 (rsl799930),857 (rs1799931) are found no statistical difference in population distribution or regional distribution (P>0.05); Population distribution in CYP2E1RsaI genotype found a statistically significant between different gender, ethnic (P<0.05); GSTM1 genotypes, GSTM1-GSTT1 genotype had found no statistical difference in the population distribution, however, in the regional distribution found a statistically significant differences (P<0.05), we also found a statistically significant difference in GSTT1 genetic polymorphism distribution of different ethnic groups (P<0.05), however, between different gender, age, smoking, drinking alcohol are found no statistical difference (P>0.05).3) From Systematic review in Chinese han people, wild genetype (44.4%) was found as a major genotype in NAT2 metabolic phenotype; The frequency of NAT2 metabolic phenotype in the middle type acetylation was the highest (44.1%), followed by fast acetylated type (39.6%); The frequency of CYP2E1RsaI genotype was found wild type was the highst (63.3%), heterozygosis type was second (31.5%), In han people also have the same characteristics, the CYP2E1RsaI genotype frequency in wild type, heterozygosis type frequency were 63.2%,31.3% respectively; From Systematic review in all Chinese people, The frequency of GSTM1 homozygous null genotypes, GSTT1 homozygous null genotypes and GSTM1-GSTT1 combined genotypes were 55.8%,48.9% and 26.4%.From Systematic review in Chinese han people, GSTM1 and GSTT1 combined genotypes were 54.2%, 47.7% and 26.1%, respectively.4) Compared tuberculosis patients with healthy people, we found that the han people of NAT2 metabolic phenotype and GSTM1 genotypes in two groups have a significant differences (P<0.05). Found in kazak people GSTT1 genotype, GSTM1-GSTT1 genotype in tuberculosis patients and healthy peopl have a significant differences (P<0.05). And in the Uighur population drug metabolic enzyme genes and its metabolic phenotype between tuberculosis patients and healthy people are found no statistical difference (P>0.05). Conclusion:1) Our study in Xinjiang province NAT2, CYP2E1RsaI, GST are showed polymorphism.The drug metabolic enzyme genes in Xinjiang province is not affected by age, sex, smoking, drinking alcohol, but with racial specificity and regional differences.2) NAT2 distribution of han Chinese in China is predominated by wild type/fast metabolic type, CYP2E1RsaI gene is predominated by wild type, GSTM1 is predominated by null genotype and GSTT1 is predominated by non-deletion genotype.3) The polymorphism distribution of NAT2 acetylated phenotype, CYP2E1RsaI and GST gene have a big racial difference; The differences between Xinjiang tuberculosis patients study and systematic review results could be due to systematically review sample size is larger.Moreover, the systematic review are largely from for the South. |
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