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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (4) : 507-516    https://doi.org/10.1007/s11684-016-0475-6
RESEARCH ARTICLE
DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese
Wei Wang1,2,3,Ming Li1,2,Li Wang3,Xueqing Yu1,2()
1. Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
2. Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou 510080, China
3. Department of Nephrology, Sichuan Provincial People’s Hospital, Chengdu 610072, China
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Abstract

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown the ethnic-specific association between certain human leukocyte antigen (HLA) alleles and IgAN susceptibility. This study was designed to explore the relationship between HLA-DQB1 alleles and disease susceptibility and clinical manifestations of patients with IgAN in southern Han Chinese. A PCR sequence-based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients and 229 healthy subjects. Clinical data were collected from each patient at the time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and healthy subjects. High frequency of HLA-DQB1*060101 and low frequency of HLA-DQB1*030101 were observed in IgAN patients compared with healthy controls. Further stratification analysis revealed that the frequency of DQB1*060101 was significantly higher in patients with urine protein≥1.0 g/24 h than in patients with urine protein<1.0 g/24 h. In combination with our previous DRB1 results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101-DQB1*020101 was significantly lower (OR= 0.194, Pc = 0.016) compared with healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a potential predictor of high-risk IgAN susceptibility in Chinese Han population.

Keywords DQB1      human leukocyte antigen (HLA)      IgA nephropathy      haplotype      association study     
Corresponding Author(s): Xueqing Yu   
Just Accepted Date: 19 October 2016   Online First Date: 23 November 2016    Issue Date: 01 December 2016
 Cite this article:   
Wei Wang,Ming Li,Li Wang, et al. DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese[J]. Front. Med., 2016, 10(4): 507-516.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0475-6
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I4/507
Variable IgAN (n, total= 217) Healthy subjects (n, total= 229)
Age (year) 33.7±16.00 34.2±17.80
Sex
Male 91 (42.30%) 106 (46.40%)
Female 126 (57.70%) 123 (53.60%)
Blood pressure
Hypertension 54 (24.88%)
Norma blood pressure 163 (75.12%) 229 (100%)
Content of urine protein
≥1.0 g/24 h 80 (36.86%)
<1.0 g/24 h 137 (63.14%) Negative
Gross hematuria
Yes 70 (32.25%)
No 147 (67.75%) 229 (100%)
Serum IgA level
>3.45 mmol/L 61 (28.11%)
≤3.45 mmol/L 156 (71.89%)
Renal function
GFR≤60 ml/min 48 (22.11%)
GFR>60 ml/min 169 (77.89%) 229 (100%)
Crescent formation
Yes 59 (27.18%)
No 158 (72.82%) 229 (100%)
Tab.1  Basic clinical characteristics of IgAN patients
DQB1 allele IgAN
(Total= 217 × 2)
Control
(Total= 229 × 2)
c2 P OR 95% CI
n % n %
Lower Upper
*020101/0202 52 11.98 52 11.35 0.035 0.835 1.063 0.706 1.600
*030101/0309 52 11.98 93 20.30 10.139 0.001a 0.534 0.370 0.772
*030201 19 4.37 15 3.27 0.469 0.390 1.352 0.678 2.690
*030302 63 14.51 49 10.69 2.62 0.085 1.417 0.951 2.112
*0304 1 0.23 3 0.65 ND ND ND ND ND
*0310 2 0.46 1 0.21 ND ND ND ND ND
*0312 0 0 2 0.42 ND ND ND ND ND
*0401 18 4.14 13 2.83 0.782 0.361 1.481 0.717 3.061
*0402 7 1.61 6 1.31 0.100 0.784 1.235 0.412 3.704
*050101 15 3.45 17 3.71 0.010 0.859 0.929 0.458 1.883
*050201 58 13.36 80 17.46 2.564 0.096 0.729 0.505 1.052
*050202 2 0.46 4 0.87 0.932 0.687 0.525 0.096 2.884
*050301 25 5.76 34 7.42 0.747 0.347 0.762 0.447 1.300
*050302 2 0.46 3 0.65 ND ND ND ND ND
*0505 1 0.23 4 0.87 ND ND ND ND ND
*060101 90 20.73 51 11.13 14.725 <0.0001b 2.088 1.439 3.030
*0602 13 2.99 13 2.83 0 1 1.057 0.484 2.306
*0604 4 0.92 8 1.74 0.606 0.387 0.523 0.156 1.750
*060502 1 0.23 0 0 ND ND ND ND ND
*0609 9 2.07 10 2.18 0 0.910 0.949 0.382 2.358
Tab.2  Distribution of HLA-DQB1 allele frequencies in IgAN patients and healthy controls
DQB1 allele 24 h proteinuria>1 g
(Total= 80 × 2)
24 h proteinuria≤1 g
(Total= 137 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 20 12.50 32 11.67 0.010 0.800 1.080 0.595 1.961
*030101/0309 14 8.75 38 13.86 2.048 0.106 0.596 0.312 1.137
*030201 5 3.12 14 5.10 0.535 0.330 0.599 0.212 1.695
*030302 22 13.75 41 14.96 0.042 0.728 0.906 0.518 1.585
*0304 1 0.62 0 0 ND ND ND ND ND
*0310 1 0.62 1 0.36 ND ND ND ND ND
*0401 6 3.75 12 4.37 0.005 0.749 0.851 0.313 2.312
*0402 3 1.87 4 1.45 0 0.712 1.129 0.285 5.838
*050101 7 4.37 8 2.91 0.584 0.391 2.14 0.425 10.779
*050201 13 8.12 45 16.42 5.213 0.011a 0.450 0.235 0.863
*050202 1 0.62 1 0.36 ND ND ND ND ND
*050301 9 5.62 16 5.83 0 0.926 0.961 0.415 2.28
*050302 0 0 2 0.72 ND ND ND ND ND
*0505 1 0.62 0 0 ND ND ND ND ND
*060101 48 30 42 15.32 12.351 <0.0001b 2.367 1.437 3.794
*0602 5 3.12 8 2.91 0 0.904 1.073 0.345 3.336
*060502 0 0 1 0.36 ND ND ND ND ND
*0604 0 0 4 1.45 ND ND ND ND ND
*0609 4 2.5 5 1.82 0.016 0.634 1.379 0.365 5.213
Tab.3  Distribution of HLA-DQB1 alleles in IgAN patients with 24 h proteinuria>1 g or≤1 g
DQB1 allele Crescent formation
(Total= 59 × 2)
No crescent formation
(Total= 158 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 13 11.01 39 12.34 0.045 0.868 0.879 0.451 1.713
*030101/0309 10 8.47 42 13.29 1.461 0.156 0.604 0.293 1.247
*030201 5 4.23 14 4.43 0 0.93 0.954 0.336 2.711
*030302 13 11.01 50 15.82 1.235 0.224 0.659 0.344 1.263
*0304 0 0 1 0.31 ND ND ND ND ND
*0310 0 0 2 0.62 ND ND ND ND ND
*0401 13 11.01 5 1.58 16.917 <0.0001a 7.701 2.682 22.114
*0402 3 2.54 4 1.26 0.261 0.369 2.035 0.449 9.231
*050101 9 7.62 6 1.89 6.820 0.007b 4.266 1.484 12.262
*050201 17 14.40 41 12.97 0.054 0.698 1.129 0.614 2.077
*050202 1 0.84 1 0.31 ND ND ND ND ND
*050301 5 4.23 20 6.32 0.361 0.391 0.655 0.24 1.787
*050302 0 0 2 0.62 ND ND ND ND ND
*0505 1 0.84 0 0 ND ND ND ND ND
*060101 22 18.64 68 21.51 0.275 0.507 0.836 0.489 1.428
*0602 4 3.38 9 2.84 0 0.771 1.197 0.361 3.963
*0604 0 0 4 1.26 ND ND ND ND ND
*060502 0 0 1 0.31 ND ND ND ND ND
*0609 2 1.69 7 2.21 0 0.730 0.761 0.156 3.717
Tab.4  Distribution of HLA-DQB1 alleles in IgAN patients with or without crescent formation
DQB1 allele Gross hematuria
(Total= 70 × 2)
No gross hematuria
(Total= 147 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 18 12.85 34 11.56 0.053 0.698 1.128 0.613 2.077
*030101/0309 14 10 38 12.92 0.517 0.380 0.749 0.391 1.432
*030201 6 4.28 13 4.42 0 1 0.957 0.324 2.824
*030302 20 14.28 43 14.62 0 1 0.973 0.548 1.726
*0304 0 0 1 0.34 ND ND ND ND ND
*0310 0 0 2 0.68 ND ND ND ND ND
*0401 8 5.71 10 3.40 0.761 0.259 1.721 0.664 4.461
*0402 6 5.45 1 0.34 6.984 0.003a 13.119 1.564 110.051
*050101 6 4.28 9 3.06 0.138 0.514 1.418 0.495 4.065
*050201 18 12.85 40 13.6 0.004 0.830 0.937 0.516 1.702
*050202 0 0 2 0.68 ND ND ND ND ND
*050301 7 5 18 6.12 0.062 0.639 0.807 0.329 1.979
*050302 0 0 2 0.68 ND ND ND ND ND
*0505 0 0 1 0.34 ND ND ND ND ND
*060101 31 22.14 59 20.06 0.318 0.618 1.133 0.694 1.850
*0602 2 1.42 11 3.74 1.041 0.186 0.373 0.082 1.705
*0604 0 0 4 1.22 ND ND ND ND ND
*060502 1 0.71 0 0 ND ND ND ND ND
*0609 3 2.14 6 2.04 0 0.944 1.051 0.259 4.266
Tab.5  Distribution of HLA-DQB1 alleles in IgAN patients with or without gross hematuria
DQB1 allele Hypertension
(Total= 54 × 2)
Normal blood pressure
(Total= 163 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 8 7.40 44 13.49 2.304 0.123 0.513 0.233 1.126
*030101/0309 10 9.25 42 12.88 0.696 0.315 0.690 0.334 1.427
*030201 3 2.77 16 4.90 0.444 0.348 0.554 0.158 1.938
*0304 0 0 1 0.30 ND ND ND ND ND
*030302 20 18.51 43 13.19 1.452 0.173 1.496 0.836 2.677
*0310 0 0 2 0.61 ND ND ND ND ND
*0401 3 2.77 15 4.60 0.297 0.410 0.592 0.168 2.087
*0402 0 0 7 2.14 ND ND ND ND ND
*050101 4 3.70 11 3.37 0 0.871 1.101 0.343 3.533
*050201 16 14.81 42 12.88 0.121 0.609 1.176 0.631 2.190
*050202 2 1.85 0 0 ND ND ND ND ND
*050301 5 4.62 20 6.13 0.118 0.552 0.743 0.272 2.029
*050302 1 0.92 1 0.30 ND ND ND ND ND
*0505 0 0 1 0.30 ND ND ND ND ND
*060101 29 26.85 61 18.71 2.794 0.076 1.595 0.959 2.652
*0602 3 2.77 10 3.06 0 0.878 0.903 0.244 3.343
*060502 1 0.92 0 0 ND ND ND ND ND
*0604 1 0.92 3 0.92 ND ND ND ND ND
*0609 2 1.85 7 2.14 0 0.852 0.860 0.176 4.203
Tab.6  Distribution of HLA-DQB1 alleles in IgAN patients with hypertension or normal blood pressure
DQB1 allele Serum IgA>3.45 mmol/L
(Total= 61 × 2)
Serum IgA≤3.45 mmol/L
(Total= 156 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 11 9.01 41 13.14 1.051 0.255 0.655 0.325 1.321
*030101/0309 14 11.47 38 12.17 0.001 1 0.935 0.487 1.794
*030201 5 4.09 14 4.48 0 0.858 0.91 0.32 2.582
*030302 25 20.49 38 12.17 4.237 0.032 1.858 1.067 3.238
*0304 0 0 1 0.32 ND ND ND ND ND
*0310 1 0.81 1 0.32 ND ND ND ND ND
*0401 6 4.91 12 3.84 0.056 0.599 1.293 0.474 3.526
*0402 2 1.63 5 1.6 0 0.978 1.023 0.196 5.346
*050101 6 4.91 9 2.88 0.563 0.313 1.741 0.606 5.001
*050201 14 11.47 44 14.1 0.321 0.532 0.79 0.416 1.5
*050202 2 1.63 0 0 ND ND ND ND ND
*050301 8 6.55 17 5.44 0.047 0.660 1.218 0.511 2.900
*050302 0 0 2 0.64 ND ND ND ND ND
*0505 1 0.81 0 0 ND ND ND ND ND
*060101 20 16.39 70 22.43 1.598 0.155 0.678 0.392 1.173
*0602 4 3.27 9 2.88 0 0.763 1.141 0.345 3.777
*0604 1 0.81 3 0.96 ND ND ND ND ND
*060502 0 0 1 0.32 ND ND ND ND ND
*0609 2 1.63 7 2.24 0.001 0.684 0.726 1.149 3.545
Tab.7  Distribution of HLA-DQB1 alleles in IgAN patients with serum IgA>3.45 or≤3.45 mmol/L
DQB1 allele eGFR≤60 ml/min/1.73m2
(Total= 48 × 2)
eGFR>60 ml/min/1.73m2
(Total= 169 × 2)
c2 P OR 95% CI
n % n % Lower Upper
*020101/0202 8 8.33 44 13.01 1.143 0.196 0.607 0.276 1.339
*030101/0309 12 12.5 40 11.83 0 0.861 1.064 0.534 2.120
*030201 5 5.20 14 4.14 0.028 0.659 1.272 0.446 3.624
*030302 18 18.75 45 13.31 1.370 0.193 1.503 0.824 2.740
*0304 0 0 1 0.29 ND ND ND ND ND
*0310 1 1.04 1 0.29 ND ND ND ND ND
*0401 5 5.20 13 3.84 0.09 0.564 1.374 0.477 3.954
*0402 2 2.08 5 1.47 0 0.708 1.383 0.264 7.243
*050101 4 4.16 11 3.25 0.013 0.673 1.292 0.402 4.154
*050201 14 14.58 44 13.01 0.052 0.734 1.141 0.596 2.184
*050202 1 1.04 1 0.29 ND ND ND ND ND
*050301 6 6.25 19 5.62 0 0.806 1.119 0.434 2.886
*050302 0 0 2 0.58 ND ND ND ND ND
*0505 0 0 1 0.29 ND ND ND ND ND
*060101 14 14.58 76 22.48 0.829 0.377 0.717 0.386 1.332
*0602 4 4.16 9 2.66 2.380 0.082 5.89 0.316 1.096
*0604 0 0 4 1.18 ND ND ND ND ND
*060502 0 0 1 0.29 ND ND ND ND ND
*0609 2 2.08 7 2.07 0 1 1.006 0.206 4.924
Tab.8  Distribution of HLA-DQB1 alleles in IgAN patients with eGFR≤60 or>60 ml/min/ 1.73 m2
DRB1-DQB1 IgAN patients
(Total = 139)
(278 alleles)
Healthy subjects
(Total= 143)
(286 alleles)
P OR 95% CI
n % n % Lower Upper
*030101-020101 6 2.15 9 3.14 0.603 0.679 0.238 1.933
*070101-020101 4 1.43 20 6.99 0.001a 0.194 0.065 0.576
*070101-030302 2 0.71 10 3.49 0.046 0.200 0.043 0.921
*080302-060101 12 4.31 14 4.89 0.842 0.876 0.398 1.930
*090102-030101 7 2.51 15 5.24 0.146 0.467 0.187 1.163
*090102-060101 24 8.63 6 2.09 0.001b 4.409 1.774 10.961
*090102-030302 6 2.15 8 2.79 0.828 0.767 0.263 2.238
*110101-050101 7 2.51 8 2.79 1.000 0.898 0.321 2.509
*120101-030101 2 0.71 8 2.79 0.107 0.252 0.053 1.196
*140101-050301 5 1.79 9 3.14 0.448 0.564 0.187 1.703
*140101-050201 3 1.07 10 3.49 0.103 0.301 0.082 1.106
*140501-020101 7 2.51 12 4.19 0.384 0.590 0.229 1.521
*150101-030302 14 5.03 12 4.19 0.783 1.211 0.550 2.666
*150101-060101 10 3.59 6 2.09 0.413 1.741 0.624 4.857
*150101-0602 6 2.15 10 3.49 0.482 0.609 0.218 1.698
*160201-050201 4 1.43 8 2.79 0.383 0.507 0.151 1.704
Others 159 121
Tab.9  HLA-DRB1-DQB1 haplotypes in IgAN patients and healthy controls
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