| Objective This paper aims to investigate expression levels of FAM102 A, ACTA2, APOL6, DHRS9,ASAP1, SLC11A1 in tuberculosis patients infected, close contacts group and healthy controls, to explore its potential as a biomarker for diagnosis of tuberculosis.The SLC11A1, ASAP1 alleles in patients with tuberculosis and health individuals were examined, which was attempted to investigate the association between the polymorphism of SLC11A1 gene and pulmonary tuberculosis in Uygur population in Xinjiang Kashi area.Methods 1.Selected subjects from the hospital, and collected 30 patients with pulmonary tuberculosis from hospital patients, and choose 18 cases of close contacts group form TB patients families and physical examination. 30 cases of healthy controls selected from a physical examination. Sodium citrate tubes were used to take 2ml peripheral venous blood of each subjects, and was extracted total RNA from the whole blood leukocytes, and finally, using Prime Script TM RT reagent Kit with g DNA Eraser conduct RNA reverse transcriptase. The expression level of FAM102 A, ACTA2, APOL6, DHRS9, ASAP1, SLC11A1 are detected by reverse transcription- quantitative PCR. Statistical analysis of measurement data using mean ±SD, ANOVA comparing RNA differences between multiple groups, P <0.05 was considered statistically significant. 2. 644 Uighurs people were selected, including 251 TB patients, 393 healthy controls, and the individual DNA samples were extracted. High-resolution typing of SLC11A1, ASAP1 was performed by the sequence-based typing(SBT) method using the SLC11A1, ASAP1 generic DNA typing kit. SLC11A1,ASAP1 gene polymorphisms associated with susceptibility to tuberculosis in the Uighur population was studied. Gene frequency differences of SNPs in Uighur samples and reported from the han samples and kazak were compared.Results 1 The expression of FAM102 A, SLC11A1, ASAP1 were downregulation in active pulmonary tuberculosis patient for 0.23 times, 0.38 times and 0.52 times compared with healthy controls,and DHRS9 were upregulation for 1.84 times.The difference was statistically significant(p <0.05 for all). The expression of ACTA2, APOL6 were no statistically significant(p >0.05). Compared with close contacts group, the expression of FAM102 A, SLC11A1, ASAP1 were downregulate for 0.45 times, 0.64 times and0.63 times compared with healthy controls, the difference was statistically significant(p <0.05). Active pulmonary tuberculosis patient of FAM102 A, SLC11A1 were downregulation for 0.50 and 0.59 times compared with close contacts group, the difference was statistically significant(p <0.05). ROC analysis of active pulmonary tuberculosis patient of FAM102 A, DHRS9, SLC11A1, ASAP1 were 0.831, 0.863, 0.841,0.848 compared with health to controls. ROC analysis of close contacts group of FAM102 A, SLC11A1,ASAP1 were 0.854, 0.813, 0.836 compared with health to controls. 2 As the results showed that the SLC11A1 gene rs17235409 GG, GA, AA genotype frequencies were 84.9%, 13.9%, AA 1.2% in Uighur samples; while in the healthy control group were 87.3%, 12.2%, 0.5%, which was no statistical significance(P > 0.05). SLC11A1 gene rs17235416 TTGG / TTGG, TTGG /-,- /- genotype frequencies in case group were 85.5%, 13.1%, 1.6%, respectively, and in healthy control group were 87.0%, 12.5%, 0.5%,respectively, which was no significant difference. SLC11A1 gene rs3731865 CC, CG, GG genotype frequencies in case group were 2%, 21.9%, 76.1%; and in healthy control group were 2.3%, 24.9%, 72.8%,which was no statistical significance(P > 0.05). SLC11A1 gene rs17235409 GG, GA, AA genotype frequencies, in this study and in reported Uighurs and Han, were 86.6%, 12.9%, 0.8% and 77.7%, 20.4%,1.9%, respectively, which was statistically significant(P <0.05). rs17235416 TGTG/TGTG,TGTG/-,--/--genotype frequencies, in this study and in the reported Uighurs and Kazakh, were 86.3%, 12.7%, 0.9% and71.9%,24.5%,3.5%, respectively, and the differences were statistically significant(P < 0.05). The ASAP1 gene rs12680942 GG, GA, AA genotype frequencies were 18.7%, 56.6%, 24.7% in Uighur samples; while in the healthy control group were 19.9%, 47.7%, 32.4%.When the CC/CA homozygote genotype was used as the reference group, the AA genotype frequencies was 24.7% in Uighur samples, while in the healthy control group was 32.4%. Stratification analyses showed that ASAP1 gene rs12680942 G> A, AA genotype frequencies were significantly different between the ages of 60 and less than non-smokers of the case group and the healthy control group, after adjustment OR values were 0.764, 0.799, 95% confidence intervals were 0.587-0.993, 0.646-0.988, P <0.05. ASAP1 gene rs4733781 C> A,the recessive gene group CC / CA genotype frequency reference, AA genotype frequencies between 60 and younger than non-smokers of cases and healthy controls significantly different, OR values were adjusted to 0.759, 0.795, 95% confidence intervals were 0.584-0.986, 0.643-0.983, P <0.05.Conclusion The expression levels of FAM102, SLC11A1, ASAP1, DHRS9 were differences in healthy controls and active tuberculosis, the expression levels of FAM102 A, SLC11A1 were differences in latent tuberculosis infection and active tuberculosis, the expression levels of FAM102 A, SLC11A1, ASAP1 were differences in latent tuberculosis infection and healthy controls. Speculated that FAM102, SLC11A1,ASAP1, DHRS9 have differentially expressed in different patients, there is a certain relationship with the occurrence and development in tuberculosis which may be a potential diagnosis biomarkers to distinguish healthy controls, active tuberculosis and latent tuberculosis infection. Polymorphisms of SLC11A1 gene are not associated with susceptibility to tuberculosis in the Uighurs. There are significant differences between the Uighur and Han and Kazak in SLC11A1 gene polymorphism loci rs17235409 rs, 17235416 genotype frequencies. A significantly decreased risk of active tuberculosis associated with the ASAP1 rs12680942G>A,rs4733781 C>A, AA polymorphism was evident among younger patients and patients who never smoking. |
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