Background
Methods
Study population
Genotyping of HLA-G gene polymorphisms
Statistical analysis
Results
Characteristics of the study population
Parameters | Patients N = 99 (%) | Healthy siblings N = 126 (%) | |
---|---|---|---|
Age, in years (mean ± SD) | 11.2 ± 2.5 | 12.2 ± 4.3 | |
Gender | |||
Male | 52 (52.5) | 75 (59.5) | |
Female | 47 (47.5) | 51 (40.5) | |
Patient classification | |||
Rheumatic Fever | 10 (10.1) | ||
Valvular Lesions | |||
MVL
| 67 (67.7) | ||
Mitral Regurgitation | Mild | 24 (35.8) | |
Moderate - Severe | 35 (52.2) | ||
MR with MS
| 3 (4.5) | ||
Mild MR, Mild MS | 1 (33.3) | ||
Moderate MR, Mild MS | 2 (66.7) | ||
MR with chorea
| 5 (7.5) | ||
Mild MR with chorea | 4 (80.0) | ||
Moderate MR with chorea | 1 (20.0) | ||
CVL
| 22 (22.2) | ||
MR, AR
| 17 (77.3) | ||
Mild MR, Mild AR | 6 (35.3) | ||
Moderate MR, Mild AR | 6 (35.3) | ||
Moderate MR, Mod AR | 1 (5.9) | ||
Severe MR, Mild AR | 3 (17.6) | ||
Severe MR, Mod AR | 1 (5.9) | ||
MR, TR
| 2 (9.1) | ||
Severe MR, Mild TR | 2 (100) | ||
MR, MS, AR
| 3 (13.6) | ||
Mild MR, Severe MS, Mild AR | 1 (33.3) | ||
Mod MR, Mod MS, Mild AR | 2 (66.7) |
Transmission disequilibrium test (TDT)
T | UT |
χ
2
|
p value | |
---|---|---|---|---|
14 bp Ins/Del | ||||
Del allele | 32 | 28 | 0.267 | 0.6056 |
+3142 C/G | ||||
G allele | 27 | 23 | 0.320 | 0.5716 |
Haplotypes | ||||
Ins/G | 28 | 31 | 0.152 | 0.6969 |
Del/G | 28.5 | 20.5 | 1.295 | 0.2552 |
Del/C | 23.5 | 27.5 | 0.309 | 0.5782 |
Linkage disequilibrium analysis
Genotype and Allele distribution in RHD patients and healthy siblings
Pooled | Male | Female | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients (99) n (%) | Healthysiblings (126) n (%) | OR (95% CI) | pc
| Patients (52) n (%) | Healthy siblings (75) n (%) | OR (95% CI) | pc
| Patients (47) n (%) | Healthy siblings (51) n (%) | OR (95% CI) | pc
| |
14 bp Ins/Del | ||||||||||||
Genotypes | ||||||||||||
Ins/Ins | 16 (16.2) | 27 (21.4) | 0.71 (0.36-1.40) | 0.4084 | 9 (17.3) | 24 (32.0) | 0.44 (0.18-1.04) | 0.0987 | 7 (14.9) | 3 (5.9) | 2.86 (0.69-11.77) | 0.2418 |
Del/Del | 35 (35.3) | 36 (28.6) | 1.37 (0.78-2.40) | 0.3128 | 18 (34.6) | 19 (25.3) | 1.53 (0.71-3.32) | 0.3755 | 17 (36.2) | 17 (33.3) | 1.17 (0.51-2.68) | 0.8791 |
Ins/Del | 48 (48.5) | 63 (50.0) | 0.94 (0.55-1.59) | 0.9272 | 25 (48.1) | 32 (42.7) | 1.24 (0.61-2.53) | 0.6734 | 23 (48.9) | 31 (60.8) | 0.62 (0.28-1.38) | 0.3296 |
Alleles | ||||||||||||
Ins | 80 (40.4) | 117 (46.4) | 0.78 (0.54-1.14) | 0.2368 | 43 (41.3) | 80 (53.3) | 0.62 (0.37-1.02) | 0.0797 | 37 (39.4) | 37 (36.3) | 1.14 (0.64-2.03) | 0.7657 |
Del | 118 (59.6) | 135 (53.6) | 1.28 (0.88-1.86) | 0.2368 | 61 (58.7) | 70 (46.7) | 1.62 (0.98-2.70) | 0.0797 | 57 (60.6) | 65 (63.7) | 0.88 (0.49-1.56) | 0.7657 |
+3142 C/G | ||||||||||||
Genotypes | ||||||||||||
C/C | 12 (12.1) | 6 (4.8) | 2.76 (0.99-7.63) | 0.0763a
| 7 (13.5) | 3 (4.0) | 3.68 (0.90-14.98) | 0.1121 | 5 (10.6) | 3 (5.9) | 1.94 (0.44-8.62) | 0.6041 |
G/G | 48 (48.5) | 66 (52.4) | 0.86 (0.50-1.45) | 0.6556 | 27 (51.9) | 44 (58.7) | 0.76 (0.37-1.55) | 0.5680 | 21 (44.7) | 22 (43.1) | 1.06 (0.48-2.37) | 0.9602 |
C/G | 39 (39.4) | 54 (42.8) | 0.87 (0.51-1.48) | 0.6985 | 18 (34.6) | 28 (37.3) | 0.87 (0.41-1.82) | 0.8556 | 21 (44.7) | 26 (51.0) | 0.81 (0.37-1.78) | 0.7431 |
Alleles | ||||||||||||
C | 63 (31.8) | 66 (26.2) | 1.31 (0.87-1.98) | 0.2280 | 32 (30.8) | 34 (22.7) | 1.52 (0.86-2.66) | 0.1927 | 31 (33.0) | 32 (31.4) | 1.08 (0.59-1.96) | 0.9302 |
G | 135 (68.2) | 186 (73.8) | 0.76 (0.50-1.15) | 0.2280 | 72 (69.2) | 116 (77.3) | 0.66 (0.37-1.16) | 0.1927 | 63 (67.0) | 70 (68.6) | 0.93 (0.51-1.69) | 0.9302 |
Haplotypes | ||||||||||||
Ins/G | 80 (40.4) | 117 (46.4) | 0.78 (0.54-1.40) | 0.2368 | 43 (41.3) | 80 (53.3) | 0.62 (0.37-1.02) | 0.0797 | 37 (39.4) | 37 (36.3) | 1.14 (0.64-2.03) | 0.7657 |
Del/G | 55 (27.8) | 69 (27.4) | 1.02 (0.67-1.55) | 0.9898 | 29 (27.9) | 36 (24.0) | 1.22 (0.69-2.16) | 0.5813 | 26 (27.6) | 33 (32.3) | 0.80 (0.43-1.48) | 0.5756 |
Del/C | 63 (31.8) | 66 (26.2) | 1.31 (0.87-1.98) | 0.2280 | 32 (30.8) | 34 (22.7) | 1.49 (0.85-2.62) | 0.2148 | 31 (33.0) | 32 (31.4) | 1.11 (0.61-2.01) | 0.8567 |
Healthy Siblings (126) n (%) | RF 10 n (%) | OR (95% CI) | pc
| MVL 67 n (%) | OR (95% CI) | pc
| CVL 22 n (%) | OR (95% CI) | pc
| |
---|---|---|---|---|---|---|---|---|---|---|
14 bp Ins/Del | ||||||||||
Genotypes | ||||||||||
Ins/Ins | 27 (21.4) | 2 (20.0) | 0.92 (0.18-4.57) | 0.7680 | 9 (13.4) | 0.57 (0.25-1.29) | 0.2446 | 5 (22.7) | 1.08 (0.36-3.19) | 0.8854 |
Del/Del | 36 (28.6) | 2 (20.0) | 0.62 (0.13-3.09) | 0.8294 | 24 (35.8) | 1.39 (0.74-2.62) | 0.3829 | 9 (40.9) | 1.73 (0.68-4.40) | 0.3630 |
Ins/Del | 63 (50.0) | 6 (60.0) | 1.5 (0.40-5.57) | 0.7792 | 34 (50.8) | 1.03 (0.57-1.86) | 0.9581 | 8 (36.4) | 0.57 (0.22-1.46) | 0.3421 |
Alleles | ||||||||||
Ins | 117 (46.4) | 10 (50.0) | 1.15 (0.46-2.86) | 0.9399 | 52 (38.8) | 0.73 (0.48-1.12) | 0.1837 | 18 (40.9) | 0.80 (0.42-1.53) | 0.6070 |
Del | 135 (53.6) | 10 (50.0) | 0.87 (0.35-2.15) | 0.9399 | 82 (61.2) | 1.37 (0.89- 2.09) | 0.1837 | 26 (59.1) | 1.25 (0.65-2.40) | 0.6070 |
+3142 C/G | ||||||||||
Genotypes | ||||||||||
C/C | 6 (4.8) | 0 | 0 | 0.9250 | 7 (10.5) | 2.33 (0.75-7.25) | 0.2306 | 5 (22.7) | 5.88 (1.62-21.39) |
0.0116
a
|
G/G | 66 (52.4) | 4 (40.0) | 0.61 (0.16-2.25) | 0.6705 | 34 (50.7) | 0.94 (0.52-1.69) | 0.9481 | 10 (45.5) | 0.76 (0.30-1.89) | 0.7124 |
C/G | 54 (42.8) | 6 (60.0) | 2.0 (0.54-7.44) | 0.4714 | 26 (38.8) | 0.84 (0.46-1.55) | 0.6962 | 7 (31.8) | 0.62 (0.24-1.63) | 0.4618 |
Alleles | ||||||||||
C | 66 (26.2) | 6 (30.0) | 1.21 (0.44-3.27) | 0.9136 | 40 (29.9) | 1.20 (0.75-1.90) | 0.5174 | 17 (38.6) | 1.78 (0.91-3.46) | 0.1300 |
G | 186 (73.8) | 14 (70.0) | 0.83 (0.30-2.24) | 0.9136 | 94 (70.1) | 0.83 (0.52-1.33) | 0.5174 | 27 (61.4) | 0.56 (0.29-1.10) | 0.1300 |
Haplotypes | ||||||||||
Ins/G | 117 (46.4) | 10 (50.0) | 1.15 (0.46-2.86) | 0.9399 | 52 (38.8) | 0.73 (0.48-1.12) | 0.1837 | 18 (40.9) | 0.80 (0.42-1.53) | 0.6070 |
Del/G | 69 (27.4) | 4 (20.0) | 0.66 (0.21-2.05) | 0.6491 | 42 (31.3) | 1.21 (0.76-1.91) | 0.4835 | 9 (20.5) | 0.68 (0.31-1.49) | 0.4372 |
Del/C | 66 (26.2) | 6 (30.0) | 1.21 (0.44-3.27) | 0.9136 | 40 (29.9) | 1.19 (0.75-1.91) | 0.5174 | 17 (38.6) | 1.78 (0.91-3.46) | 0.1300 |
Study models | OR (95% CI) | pc
|
---|---|---|
CC + CG vs GGa
CC vs GGb
CC vs GG + CGc
CG vs CC + GGd
| 1.32 (0.53-3.28) 5.50 (1.41-21.44) 5.88 (1.62-21.39) 0.62 (0.24-1.63) | 0.7124
0.0261
0.0116
0.4618 |