Background
Methods
Study design
Serum 25 (OH)D assay
Genotyping
Sample size and statistical analysis
Results
Participant characteristics
Determinants of vitamin D status in cases and controls
TB cases | Control | ||||||
---|---|---|---|---|---|---|---|
Characteristics | 25 (OH) D ≤20 nmol/l | aOR(95 % CI)a | P | 25(OH) D ≤20 nmol/l | aOR(95 % CI)a | P | |
Age | >30 years | 56/124 (45 %) | Ref | 17/50 (34 %) | Ref | ||
≤30 years | 62/136 (46 %) | 1.26(0.71-2.32) | 0.44 | 17/62 (27 %) | 1.46(0.60-3.56) | 0.40 | |
Sex | Male | 43/120 (36 %) | Ref | - | 11/58 (19 %) | Ref | - |
Female | 75/140 (54 %) | 2.31(1.33-4.01) | 0.003 | 23/54 (43 %) | 3.67(1.38-9.70) | 0.01 | |
Marital status | Single | 49/114 (43 %) | Ref | - | 16/54 (30 %) | Ref | - |
Married | 69/146 (46 %) | 1.34(0.71-2.55) | 0.36 | 18/58 (31 %) | 1.63(0.64-1.43) | 0.30 | |
Monthly income, PKR | <10,000 | 84/177 (47 %) | 1.27(0.73-2.20) | 0.38 | 18/62 (29 %) | 1.0(0.42-2.40) | 0.98 |
≥10,000 | 34/83 (41 %) | Ref | - | 16/50 (32 %) | Ref | - | |
Month of recruitment | April-September | 53/137 (39 %) | Ref | - | 10/53 (19 %) | Ref | - |
October-March | 65/123 (53 %) | 1.89(1.14-3.16) | 0.01 | 24/59 (41 %) | 2.55(1.03-6.31) | 0.04 |
Association between phenotypic features and susceptibility to active tuberculosis
TB cases (N = 260) | Control (N = 112) | OR (95 % CI) | P | aOR(95 % CI)a | P | ||
---|---|---|---|---|---|---|---|
Age | >30 years | 124 (48 %) | 50 (45 %) | Ref | - | Ref | - |
≤30 years | 136 (52 %) | 62 (55 %) | 1.01(0.58-1.42) | 0.68 | 1.01(0.61-1.68) | 0.94 | |
Sex | Male | 120 (46 %) | 58 (52 %) | Ref | - | Ref | - |
Female | 140 (54 %) | 54 (48 %) | 1.25(0.80-1.95) | 0.31 | 1.06(0.65-1.75) | 0.79 | |
Marital status | Single | 114 (44 %) | 54 (48 %) | Ref | - | Ref | - |
Married | 146 (56 %) | 58 (52 %) | 1.19(0.76-1.86) | 0.43 | 1.13(0.67-1.90) | 0.63 | |
Monthly income, PKR | <10,000 | 177 (68 %) | 62 (55 %) | 1.72(1.10-2.71) | 0.02 | 1.68(1.06-2.66) | 0.02 |
≥10,000 | 83 (32 %) | 50 (45 %) | Ref | - | Ref | - | |
Season of recruitment | April-September | 137 (53 %) | 53 (47 %) | 1.24(0.79-1.23) | 0.34 | 1.24(0.78-1.96) | 0.34 |
October-March | 123 (47 %) | 59 (53 %) | Ref | - | Ref | - | |
Serum 25(OH)D, nmol/L | ≤20 nmol/L | 118 (45 %) | 34 (30 %) | 1.90(1.19-3.05) | 0.02 | 1.87(1.15-3.04) | 0.01 |
>20 nmol/L | 142(55 %) | 78(70 %) | Ref | - | Ref | - |
Association between vitamin D pathway genotype and susceptibility to active tuberculosis
SNP, gene | Genotype | TB cases, n/N (%) | TB contacts, n/N (%) | aOR (95 % CI)a | P |
---|---|---|---|---|---|
rs7312236, VDR | AA | 84/230 (37 %) | 42/100 (42 %) | Ref | - |
AG/GG | 146/230 (63 %) | 58/100 (58 %) | 1.22(0.75-1.98) | 0.42 | |
rs154410, VDR | CC | 53/235 (23 %) | 29/106 (27 %) | Ref | - |
CT/TT | 182/235 (77 %) | 77/106 (73 %) | 1.23(0.71-2.09) | 0.45 | |
rs228570, VDR | GG | 137/235 (59 %) | 68/107 (64 %) | Ref | - |
GA/AA | 98/235 (41 %) | 39/107 (36 %) | 1.89(0.80-2.10) | 0.28 | |
rs7041, DBP | AA | 55/232 (24 %) | 21/102 (21 %) | Ref | - |
AC/CC | 177/232 (76 %) | 81/102 (79 %) | 0.77(0.43-1.39) | 0.39 | |
rs4588, DBP | GG | 122/234 (52 %) | 50/107 (47 %) | Ref | - |
GT/TT | 112/234 (48 %) | 57/107 (53 %) | 0.93(0.58-1.49) | 0.77 | |
rs10500804, CYP2R1 | GG | 59/231 (26 %) | 22/103 (22 %) | Ref | - |
GT/TT | 172/231 (74 %) | 81/103 (78 %) | 0.83(0.47-1.47) | 0.53 | |
rs2060793, CYP2R1 | GG | 112/228 (49 %) | 51/101 (50 %) | Ref | - |
AG/AA | 116/228 (51 %) | 50/101 (50 %) | 0.91(0.56-1.48) | 0.72 | |
rs10766197, CYP2R1 | AA | 52/232 (23 %) | 19/104 (18 %) | Ref | - |
AG/GG | 124/232 (77 %) | 55/104 (82 %) | 0.68(0.37-1.26) | 0.23 |
Association between vitamin D deficiency and host genotype, stratified by vitamin D status
SNP, gene | Genotype | Serum 25(OH) D ≤20 nmol/l | Serum 25(OH) D >20 nmol/l | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
TB cases | Controls | OR(95 % CI) | P | TB cases | Control | OR(95 % CI) | P | Adjusted ratio of odds ratiosa | P interaction | ||
rs7312236, VDR | AA | 30/102(29 %) | 12/24(50 %) | Ref | - | 54/128(42 %) | 30/76(40 %) | Ref | - | Ref | - |
AG/GG | 72/102(71 %) | 12/24(50 %) | 2.40(0.96-5.94) | 0.054 | 74/128(58 %) | 46/76(60 %) | 0.89(0.50-1.59) | 0.70 | 1.65(0.59-4.58) | 0.33 | |
rs154410, VDR | CC | 16/105(15 %) | 8/25(32 %) | Ref | - | 37/130(29 %) | 21/81(26 %) | Ref | Ref | - | |
CT/TT | 89/105(85 %) | 17/25(68 %) | 2.61(0.96-7.07) | 0.052 | 93/130(71 %) | 60/81(74 %) | 0.88(0.47-1.64) | 0.68 | 2.16(0.69-6.75) | 0.18 | |
rs228570, VDR | GG | 60/105(57 %) | 13/25(52 %) | Ref | - | 77/130(59 %) | 55/82(67 %) | Ref | Ref | - | |
GA/AA | 45/105(43 %) | 12/25(48 %) | 0.81(0.33-1.94) | 0.64 | 53/130(41 %) | 27/82(33 %) | 1.40(0.78-2.5) | 0.25 | 0.48(0.17-1.29) | 0.14 | |
rs10500804, CYP2R1 | GG | 27/102(26 %) | 6/23(26 %) | Ref | - | 32/129(25 %) | 16/80(20 %) | Ref | Ref | - | |
GT/TT | 75/102(74 %) | 17/23(74 %) | 0.98(0.35-2.74) | 0.97 | 97/129(75 %) | 64/80(80 %) | 0.75(0.38-1.49) | 0.42 | 1.51(0.47-4.8) | 0.48 | |
rs2060793, CYP2R1 | GG | 48/104(46 %) | 11/22(50 %) | Ref | - | 64/124(52 %) | 40/79(51 %) | Ref | Ref | - | |
AG/AA | 56/104(54 %) | 11/22(50 %) | 1.16(0.46-2.92) | 0.74 | 60/124(48 %) | 39/79(49 %) | 0.96(0.54-1.69) | 0.89 | 1.02(0.37-2.78) | 0.96 | |
rs10766197, CYP2R1 | AA | 23/104(22 %) | 4/23(17 %) | Ref | - | 29/128(23 %) | 15/81(19 %) | Ref | Ref | - | |
AG/GG | 81/104(78 %) | 19/23(83 %) | 0.74(0.22-2.39) | 0.60 | 99/128(77 %) | 66/81(81 %) | 0.77(0.38-1.55) | 0.47 | 1.25(0.35-4.45) | 0.72 | |
rs7041, DBP | AA | 27/104(52 %) | 4/23(43.5 %) | Ref | - | 26/133(20 %) | 19/74(47 %) | Ref | Ref | - | |
AC/CC | 77/10(35 %) | 19/23(43.5 %) | 0.60(0.18-1.9) | 0.39 | 107/133(80 %) | 55/74(45 %) | 1.42(0.72-2.79) | 0.30 | 1.15(0.34-3.88) | 0.81 | |
rs4588, DBP | GG | 55/105(52 %) | 10/24(42 %) | Ref | - | 68/135(50 %) | 38/76(50 %) | Ref | - | Ref | - |
GT/TT | 50/105(48 %) | 14/24(58 %) | 0.64(0.26-1.59) | 0.34 | 67/135(50 %) | 38/76(50 %) | 0.98(0.56-1.72) | 0.95 | 0.93(0.35-2.48) | 0.89 |