HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Analysis of the Type 1 Diabetes Genetics Consortium Families
Article Figures & Tables
Tables
- TABLE 1
Descriptive characteristics of the study subjects
Ethnicity Origin Families Affected siblings per family Sex (% women) Age at onset Caucasian Australia New Zealand 14.6 (94) 2.03 ± 0.29 51.93 10.34 ± 8.08 Europe 49.4 (318) 2.01 ± 0.08 61.54 12.28 ± 4.99 North America 29.9 (193) 1.99 ± 0.20 45.18 10.66 ± 7.19 Other 0.2 (1) 2.00 ± 0.00 44.35 8.33 ± 5.93 Non-Caucasian East Asian 5.9 (38) 1.05 ± 0.23 0.00 10.50 ± 7.78 Data are % (n) or means ± SD.
- TABLE 2
Frequency distribution of DRB1-DQB1 haplotypes in Caucasian probands and in AFBAC
DRB1 DQA1 DQB1 AFBAC Proband Trans OR (95% CI) χ2 P value Effect on T1D* 0101 0101 0501 9.0 6.6 44.6 0.71 (0.52–0.98) 3.96 0.047 0101 0102 0504 0.2 0.1 50.0 0.37 (0.03–4.08) 0.70 0.40 0102 0101 0501 1.0 0.7 32.5 0.66 (0.25–1.71) 0.74 0.39 0103 0101 0501 0.6 0.1 25.0 0.15 (0.02–1.26) 3.99 0.046 0301 0501 0201 12.5 34.1 70.9 3.64 (2.89–4.58) 95.33 2 × 10−22 S3 0401 0301 0201 0.1 0.2 57.1 1.48 (0.13–16.37) 0.10 0.75 0401 0301 0301 3.9 1.4 33.6 0.35 (0.20–0.63) 12.78 4 × 10−4 0401 0301 0302 4.5 28.1 84.5 8.39 (5.97–11.80) 156.73 6 × 10−36 S2 0402 0301 0302 1.0 3.5 73.3 3.63 (1.76–7.49) 13.28 3 × 10−4 S4 0403 0301 0302 1.2 0.3 13.3 0.27 (0.08–0.84) 5.69 0.017 0404 0301 0302 3.2 5.0 57.1 1.59 (1.01–2.49) 3.88 0.049 S5 0404 0301 0402 0.1 0.2 50.0 1.48 (0.13–16.37) 0.10 0.75 0405 0301 0201 0.3 0.5 42.1 1.48 (0.37–5.95) 0.31 0.58 0405 0301 0302 0.2 2.5 87.3 11.37 (2.71–47.68) 16.88 4 × 10−5 S1 0407 0301 0301 1.4 0.2 8.0 0.11 (0.03–0.50) 11.68 6 × 10−4 0408 0301 0301 0.4 0.1 20.0 0.18 (0.02–1.65) 2.81 0.094 0408 0301 0304 0.3 0.7 56.5 1.98 (0.52–7.49) 1.03 0.31 0701 0201 0201 10.1 3.5 28.2 0.32 (0.22–0.46) 35.67 2 × 10−9 0701 0201 0303 4.3 0.1 3.6 0.02 (0.00–0.13) 48.33 4 × 10−12 P1 0801 0301 0302 0.0 0.2 71.4 2.17 0.14 0801 0401 0402 2.4 3.1 50.0 1.25 (0.73–2.14) 0.68 0.41 0803 0601 0301 0.3 0.0 0.0 0.00 3.96 0.047 0804 0401 0402 0.2 0.2 50.0 0.74 (0.10–5.26) 0.09 0.76 0901 0301 0201 0.0 0.2 100.0 1.45 0.23 0901 0301 0303 1.6 0.8 45.2 0.53 (0.23–1.19) 2.40 0.12 1001 0101 0501 0.7 0.3 26.1 0.49 (0.14–1.75) 1.22 0.27 1101 0501 0301 6.5 1.2 17.9 0.18 (0.10–0.32) 39.80 3 × 10−10 1102 0501 0301 0.4 0.2 23.1 0.37 (0.07–2.02) 1.40 0.24 1103 0501 0301 1.0 0.2 25.0 0.25 (0.07–0.91) 5.06 0.024 1104 0103 0603 0.3 0.1 12.5 0.25 (0.03–2.37) 1.69 0.19 1104 0501 0301 2.3 0.2 6.3 0.07 (0.02–0.30) 21.88 3 × 10−6 P4 1201 0501 0301 1.1 0.3 30.3 0.29 (0.09–0.94) 4.68 0.031 1301 0103 0603 5.9 0.8 14.8 0.13 (0.07–0.26) 43.59 4 × 10−11 1302 0102 0604 2.6 2.2 46.1 0.87 (0.49–1.52) 0.26 0.61 1302 0102 0609 0.3 0.0 22.2 0.00 3.96 0.047 1303 0501 0301 1.0 0.1 10.0 0.08 (0.01–0.64) 9.01 0.003 P5 1401 0101 0503 2.1 0.0 0.0 0.02 (0.00–0.32) 23.51 1 × 10−6 P2 1404 0101 0503 0.1 0.1 50.0 0.74 (0.05–11.85) 0.05 0.83 1501 0102 0501 0.2 0.0 0.0 0.00 2.64 0.10 1501 0102 0602 12.0 0.4 3.9 0.03 (0.01–0.07) 127.14 2 × 10−29 P3 1501 0102 0603 0.3 0.0 0.0 0.00 3.96 0.047 1502 0103 0601 0.7 0.2 13.3 0.25 (0.05–1.22) 3.37 0.066 1601 0102 0502 2.0 1.0 35.7 0.49 (0.23–1.02) 3.67 0.055 1602 0102 0502 0.1 0.1 50.0 0.74 (0.05–11.85) 0.05 0.83 Total 898 1,214 721.72 5 × 10−124 Data are %.
* For haplotypes with a frequency >1% in either probands or control subjects, the five most susceptible (S) and the five most protective (P) haplotypes are indicated. T1D, type 1 diabetes.
- TABLE 3
Frequency distribution of DRB1-DQB1 haplotypes in East-Asian families and in AFBAC
DRB1 DQA1 DQB1 AFBAC Proband OR (95% CI) χ2 P value 0301 0501 0201 2.8 22.4 10.08 (2.24–45.45) 11.05 0.0009 0402 0301 0302 0.0 1.3 3.83 (0.05–310.02) 0.41 0.5216 0403 0301 0302 5.6 2.6 0.46 (0.08–2.59) 0.78 0.3772 0405 0103 0503 4.2 1.3 0.31 (0.03–3.02) 1.11 0.2917 0405 0301 0401 2.8 6.6 2.46 (0.46–13.13) 1.13 0.2879 0405 0301 0402 0.0 5.3 15.94 (0.28–918.70) 3.11 0.0777 0406 0301 0302 1.4 1.3 0.95 (0.06–15.42) 0.00 0.9695 0408 0301 0304 0.0 1.3 3.83 (0.05–310.02) 0.41 0.5216 0410 0301 0302 0.0 1.3 3.83 (0.05–310.02) 0.41 0.5216 0410 0301 0402 1.4 0.0 0.23 (0.00–18.98) 0.49 0.4831 0441 0301 0302 1.4 0.0 0.23 (0.00–18.98) 0.49 0.4831 0701 0201 0201 2.8 1.3 0.47 (0.04–5.26) 0.39 0.5324 0701 0201 0303 2.8 0.0 0.12 (0.00–7.48) 1.46 0.2272 0803 0103 0601 1.4 0.0 0.23 (0.00–18.98) 0.49 0.4831 0901 0301 0303 5.6 11.8 2.28 (0.67–7.78) 1.66 0.1971 1101 0103 0601 2.8 0.0 0.12 (0.00–7.48) 1.46 0.2272 1101 0501 0301 5.6 1.3 0.23 (0.02–2.08) 1.97 0.1607 1201 0501 0301 1.4 0.0 0.23 (0.00–18.98) 0.49 0.4831 1202 0102 0502 0.0 1.3 3.83 (0.05–310.02) 0.41 0.5216 1202 0601 0301 18.1 3.9 0.19 (0.05 0.69) 6.81 0.0091 1302 0102 0609 0.0 1.3 3.83 (0.05–310.02) 0.41 0.5216 1404 0101 0503 1.4 3.9 2.92 (0.30–28.72) 0.90 0.3440 1501 0102 0502 1.4 2.6 1.92 (0.17–21.63) 0.28 0.5956 1501 0102 0602 1.4 0.0 0.23 (0.00–18.98) 0.49 0.4831 1502 0101 0501 13.9 1.3 0.08 (0.01–0.66) 7.86 0.0050 1502 0102 0502 22.2 27.6 1.34 (0.63–2.83) 0.43 0.5106 Total 72 76 44.92 0.0085 Dataare%.
- TABLE 4
Relative predispositional effects of seven DR-DQ haplotypes
Haplotype AFBAC Type 1 diabetes Association in all samples Association excluding DR3, DR4, and protective haplotypes* OR (95% CI) P value Rank OR (95% CI) P value Rank DRB1*0801 DQA1*0401 DQB1*0402 2.45 3.05 1.25 (0.73–2.14) 0.41 1 2.58 (1.48–4.48) 0.0013 1 DRB1*1302 DQA1*0102 DQB1*0604 2.56 2.23 0.87 (0.49–1.52) 0.61 2 1.72 (0.96–3.07) 0.076 2 DRB1*0101 DQA1*0101 DQB1*0501 9.02 6.60 0.71 (0.52–0.98) 0.047 3 1.55 (1.08–2.22) 0.029 3 DRB1*0901 DQA1*0301 DQB1*0303 1.56 0.82 0.53 (0.23–1.19) 0.12 4 1.00 (0.44–2.28) 0.73 4 DRB1*1601 DQA1*0102 DQB1*0502 2.00 0.99 0.49 (0.23–1.02) 0.055 5 0.93 (0.44–1.96) 0.66 5 DRB1*0401 DQA1*0301 DQB1*0301 3.90 1.40 0.35 (0.20–0.63) 4 × 10−4 6 0.65 (0.36–1.20) 0.17 6 DRB1*0701 DQA1*0201 DQB1*0201 10.10 3.50 0.32 (0.22–0.46) 2 × 10−9 7 0.58 (0.38–0.87) 0.015 7 Data are %.
* The protective haplotypes excluded are DRB1*150x DQB1*060x; all DRB1*11, -*12, -*13, and -*14 haplotypes with DQB1*0301; DRB1*140x DQB1*050x; and DRB1*0701 DQB1*0303 haplotypes.
- TABLE 5
Amino acid differences between closely related DR-DQ haplotypes that differ in type 1 diabetes risk
DRB1*1301-DQA1–0103-DQB1*0603 (OR 0.13) vs. DRB1*1302-DQA1*0102-DQB1*0604 (OR 0.87) DRB1 Val-86 Gly-86 DQA1 Arg-41 Lys-41 DQB1 Asp-57, Gly-70, Ala-86 Val-57, Arg-70, Gly-86 DRB1*0401-DQA1*0301g-DQB1*0302 (OR 8.39) vs. DQB1*0404-DQA1*0301g-DQB1*0302 (OR 1.59) DRB1 Lys-71, Gly-86 Arg-71, Val-86 DRB1*1502-DQA1*0101g-DQB1*0501 (OR 0.08) vs. DRB1*1502-DQA1*0102-DQB1*0502 (OR 1.34) DQA1 Glu-34 Gln-34 DQB1 Val-57 Ser-57 - TABLE 6
DQB1 alleles on DR4 haplotypes in DR4+ patient genotypes
Genotype DQB1*0201 DQB1*0301 DQB1*0302 DQB1*0304 DQB1*0400 Total† DR1/DR4 0.0 13.1 81.8 5.1 0.0 99 DR3/DR4 0.4 0.7 98.5 0.4 0.0 453 DR4/DR4 1.6 5.6 89.3 1.6 2.0 252 DR4/DR8 0.0 2.5 97.5 0.0 0.0 40 Data are %.
† Data are n.
- TABLE 7
DRB1*04 subtypes (alleles) in DQB1*0302+ patient genotypes
As a percentage of genotype *0401 *0402 *0403 *0404 *0405 *0406 *0407 *0408 Total† DR1/DR4 74.4 5.8 0.0 8.1 5.8 0.0 0.0 5.8 86 DR3/DR4 66.4 11.8 0.2 13.1 7.6 0.0 0.0 0.9 450 DR4/DR13 73.3 16.0 0.0 1.3 9.3 0.0 0.0 0.0 75 DR4/DR4 77.3 5.0 0.4 10.3 5.4 0.0 0.0 1.7 242 DR4/DR7 64.9 5.4 0.0 10.8 13.5 0.0 0.0 5.4 37 DR4/DR8 79.5 5.1 0.0 10.3 0.0 0.0 5.1 0.0 39 DR4/DR9 100.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 8 DR4/DRX 54.3 3.7 0.0 25.9 7.4 1.2 0.0 7.4 81 Data are %.
† Data are n.
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In this Issue
April 2008, 57(4)
HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
