A Study On The Association Of Polymorphisms Of The NRAMP1 Gene And VDR Gene With Susceptibility To Pulmonary Tuberculosis In Chinese Tibetans

Objective To investigate the association between 5'(GT)_n, INT4, D53Nand 3'UTR polymorphisms of the NRAMPlgene and susceptibility of PTB.Methods Four polymorphisms of the NRAMP1 gene were typed bydenaturalization high Performance Liquid Chromatography (DHPLC) andPCR-RFLP among 140 patients and 139 healthy contacts who had beensensitized to tuberculosis. The relationship between four polymorphismsand susceptibility of PTB were studied, and cases were grouped accordingto genotypes.Results Thegenotype (GT)₉/(GT)₉, (GT)₉/(GT)₁₀, (GT)₁₀/(GT)₁₀of 5'(GT)_n polymorphism were observed in 63 (45%), 58(41.4%) and 19 (13.6%) cases among tuberculosis group while in 88(63.3%), 41 (29.5%) and 10 (7.2%) cases among control group. Asignificant increase of genotype (GT)₁₀/(GT)₁₀ was seen in the PTBpatients when compared to controls (P＜0.01, OR 2.654, 95% confidenceinterval 1.156,6.094). The genotype of G/G of INT4 polymorphism were in127 (90.7%) cases, G/Ain 13 (9.3%) cases among patients while G/G in133 (95.7%) cases, G/C in 6(4.3%) cases among controls. No significant difference in these genotype frequencies was seen between two groups(p＞0.05, OR 2.269, 95% confidence interval 0.837, 6.152). GenotypeTGTG+/+ of 3′UTR polymorphism were in 84 (60.0%) cases, TGTG+/delin 50 (35.7%) cases and TGTG del/del in 6 (4.3%) case among patientswhile TGTG+/+ in 101 (72.7%) cases, TGTG+/de in 36 (25.9%) cases andTGTG del/del in 2 (1.4%) case among controls. No significant increase ofgenotype TGTG+/del was seen in the PTB patients when compared tocontrols (P＞0.05, OR 2.027, 95% confidence interval 1.182, 3.476). Thegenotype ofG/G ofD543N polymorphism were in 103 (73.6%) cases, G/Ain 37 (26.4%) cases among patients while G/G in 118 (84.9%) cases, G/Ain 21 (15.1%) cases among controls. The frequency of genotype G/A werefound more often among patients than that in controls(p＜0.05, OR 2.018,95% confidence interval 1.111, 3.668).5′(GT)_n and INT4 showed linkage disequilibrium and D′was 0.859.3′UTR and D543N also showed linkage disequilibrium and D′was0.821. The rest alleles were not significantly associated with each other (D′＜0.5).The frequencies of 5′(GT)₉/INT4 C, 5′(GT)₁₀/INT4 C, 5′(GT)9/INT4Gand5′(GT)₁₀/INT4Ghaplotypewere0.9%, 3.7%, 64.8%,30.6% in patients and 0%, 2.2%, 78.1%, 19.8% in controls, respectively. 5′(GT)₉/INT4 G haplotype conferred lower risk suffering from tuberculosis(p＜0.01,OR OR 0.517, 95% confidence interval 0.355,0.752 ).Thefrequencies of 3′UTR TGTG/D543N A, 3′/UTR TGTG/D543N G, 3′UTR TGTG del/D543N A, 3′UTR TGTGdel/D543N A haplotype were1.2%, 76.6%, 12.0%, 10.1% inpatients and 1.2%, 84.4%, 6.4%, 8.0% in controls, respectively. 3'UTR TGTG /D543N G haplotype was associatedwith lower tuberculosis risk(p＜0.05,OR 0.605, 95% confidence interval0.395,0.927)and 3'UTR TGTG del/D543N A haplotype was associated withlower tuberculosis risk(p＜0.05, OR 2.003, 95% confidence interval1.098,3.653).Conclusion The 5'(GT)_n and D53N polymorphism ofNRAMP1 genemight be associated with PTB in Chinese Tibetan population, but noevidences supported that the INT4 and 3' UTR polymorphism wereassociated with PTB in Tibetan. 5'(GT)_n and INT4 showed linkagedisequilibrium, so did 3′UTR and D543N. 5′(GT)₉/INT4 G, 3'UTRTGTG/D543N G haplotypes conferred lower risk suffering from tuberculosisbut 3'UTR TGTG del/D543N A haplotype conferred higher risk Objective To investigate the association between Fokâ… and Taqâ… polymorphisms of the VDR gene and susceptibility of PTB.Methods Two polymorphisms of the VDR gene were typed by PCR-RFLPamong 140 patients and 139 healthy contacts who had been sensitized totuberculosis. The relationship between two polymorphisms and susceptibilityof PTB were studied, and cases were grouped according to genotypes.Results The genotype FF, Ff, ff were observed in 60, 56 and 24 cases amongtuberculosis group while in 70, 60 and 9 cases among control group. Asignificant increase of VDR genotype ff (mutant homozygotes) was seen inthe PTB patients when compared to controls (P＜0.05, OR3.111, 95%confidence interval 1.343, 7.207). The genotype of TT were in 137 cases, Ttin 3 cases among patients while TT in 134 cases, Tt in 5 cases amongcontrols. No significant difference in these genotype frequencies was seenbetween two groups (p＞0.05, OR 1.704, 95% confidence interval 0.399,7,272). Two polymorphisms didn't show linkage disequilibrium and D' is0.475.Conclusion The Fokâ… polymorphism of VDR gene might be associated with PTB in Chinese Tibetan population, but no evidences supported that the Taqâ… polymorphism were associated with PTB in Tibetan. The twopolymorphisms didn't show linkage disequilibrium.