Tuber&
and Lung disease (1992) 73.280-284
No association or linkage with HLA-DR or -DQ genes in South Indians with pulmonary tuberculosis C. B. Sanjeevi*,
P. R. Narayanan t, R. Prabakart,
N. Charles?, B. E. Thomas?,
R. Balasubramaniamt,
0.Olerup*
Venterfor BioTechnology and Department of Clinical Immunology, Karolinska Institute, Huddinge, Sweden, and tTuberculosis Research Center, Indian Council of Medical Research, Madras, India S UMMA R Y. Studies of the HLA class II genes were performed in patients and multiple families with pulmonary tuberculosis from South India to seek any association of disease susceptibility with an individual allele or haplotype. TaqI RFLP analysis of HLA-DRB, -DQA and -DQB genes was done in 38 patients and 36 healthy control subjects. No significant association with any particular allele or haplotype was obtained. Linkage analysis performed in 12 families and haplotype sharing analysis in 9 families showed that the genetic susceptibility to pulmonary tuberculosis was not linked to the HLA region. The results suggest that the RFLP patterns of HLA class II genes DRB, DQA and DQB are not associated with susceptibility to pulmonary tuberculosis and that the genes controlling susceptibility or resistance may be located outside the HLA region. R&S U MI?. Des etudes de genes HLA classe II ont CtCentreprises chez des malades et des familles multiples
atteints de tuberculose pulmonaire en Inde du Sud, afin de chercher l’association d’une susceptibilite a la maladie avec l’existence d’allele ou d’haplotype individuels. Une analyse TaqI RFLP des genes HLA-DRB, -DQA, -DQB a CtCfaite chez 38 malades et 36 sujets temoins sains. Aucune association significative n’a CtC objectivee avec un allele ou haplotype en particulier. Une analyse de liaison entreprise dans 12 familles et une analyse de partage des haplotypes dans 9 familles ont montre que la susceptibilite genetique a la tuberculose n’etait pas like a la region HLA. Les resultats suggerent que les dispositions RFLP des genes HLA classe II, DRB, DQA et DQB ne sont pas associees a une susceptibilite a la tuberculose pulmonaire et que les genes qui controlent la susceptibilite ou la resistance doivent Ctrelocalises en dehors de la region HLA. R ES UM E N . Se realizaron estudios de genes HLA clase II en pacientes y familias con tuberculosis pulmonar
de1 Sur de la India, para buscar una asociacion de la susceptibilidad a la enfermedad con un alelo o haplotipo individual. Se realiz6 un analisis TuqI RFLP de 10s genes HLA-DRB, -DQA, -DQB en 38 pacientes y 36 controles sanos. No se obtuvo asociacion significativa con ningun alelo o haplotipo en particular. Un anilisis de ligazdn efectuado en 12 familias y un analisis de repartici6n de 10s haplotipos en 9 familias mostraron que la susceptibilidad genetica a la tuberculosis pulmonar no esti ligada a la region HLA. Los resultados sugieren que la disposici6n RFLP de 10s genes HLA clase II, DRB, DQA y DQB no estri asociada con la susceptibilidad a la tuberculosis pulmonar y que 10s genes que controlan la susceptibilidad o la resistencia podrian estar localizados fuera de la regi6n HLA.
Most genes of the major histocompatibility complex (MHC) are characterized by a high degree of allelic polymorphism. This has been determined using multiple techniques including serology, biochemical analysis, restriction fragment length polymorphism (RFLP) analysis and nucleotide sequence comparisons. Thus for the human MHC class II genes, 44 alleles of the DRBl gene, 15 of the DQBI gene and nine of the DQAl gene are currently recognized.’
The major function of the MHC molecules is to act as recognition elements for T lymphocytes, who have an obligatory requirement to co-recognize antigenic peptides with self-MHC products. Therefore, the MHC alleles inherited by an individual are one of the major determinants of the immune response phenotype. Soon after reliable techniques for the definition of human MHC alleles became available, it was noted that several diseases with a suspected immune pathogenesis were associated with human leucocyte antigens (HLA). The number of such associations rapidly increased and most of these have turned out to be associations with MHC
Correspondence to: C. B. Sanjeevi, Department of Endocrinology, Karolinska Hospital, S-104 01 Stockholm, Sweden. 280
HLA-DR and -DQ in pulmonary
class II alleles. Furthermore, the identification of nonHLA genes within the MHC and the phenomenon of linkage disequilibrium raise the possibility that a neighbouring gene of HLA or non-HLA status in linkage with the observed associated allele may be the true susceptibility gene. Tuberculosis is an infectious disease with a strong immunological basis, involving cell-mediated immunity.’ Since all T cell responses are MHC-dependent, the possible association between HLA class I and class II alleles, serologically defined, has been investigated in several studies in patients with tuberculosis. Previous studies on HLA class I alleles in patients with tuberculosis have shown positive association with B15 in American blacks,’ B15 and Bw35 in Chinese,4,5 A2 and B5 in Egyptians6 and with B8 in Canadians.’ The frequency of B 12 has decreased in Korean patients with tuberculosis.* Studies in pulmonary tuberculosis patients in European Caucasians,’ Japanese,” Mexican Americans,” South IndiansI and North Indians13 have not shown any significant correlation with the disease. Association with the HLA class II allele, DR2r4 and the linked specificity DQw 1, have been shown in patients with pulmonary tuberculosis.‘5 Insignificant increases of the occurrence of the DR2 allele have also been observed in several other ethnic group~.‘~,‘~ However, in studies on Hong Kong Chinese,” Egyptians6 no HLA-DR2 association was and black Americans,” found. The aims of the present study were two-fold, to assess association of HLA class II alleles (DR and DQ) with pulmonary tuberculosis utilizing genomic typing techniques and to perform linkage analysis in families with one parent and one child with the disease.
MATERIALS AND METHODS Subjects Patients attending the clinic of the Tuberculosis Research Centre, Madras, formed the study group. 38 unrelated patients with pulmonary tuberculosis, diagnosed on the basis of clinical, bacteriologic and radiographic evidence, were included in the study. 36 unrelated healthy volunteers, who formed the control group, were screened for tuberculosis and found negative. 12 nuclear families, in whom one of the parents and one child had the disease, were chosen for segregation analysis. Three of the 12 families were not included in the analysis of haplotype-sharing, as one of the parents was HLA class I and class II homozygous in 2 families and in a third family both parents were identical heterozygotes.
Southern blot analysis DNA was isolated from the peripheral
blood leukocytes
281
tuberculosis
using standard techniques. The isolated DNA was subjected to restriction enzyme digestions (TuqI and MspI), agarose gel electrophoresis, capillary blotting to nylon membrane, hybridization, stringency washes and autoradiography.”
TuqI DRB, DQA and DQB RFLP typing DR and DQ typing was performed by hybridizing Taql cleaved DNA with DRB, DQA and DQB cDNA probes.19 Restriction fragment patterns were analysed as previously described.“x2’ The nomenclature used is that of the serologically defined DR and DQ specificities associated with different allelic TaqI DRB-DQA-D&B haplotypes. The distinction between DR7,DQw9 and DR9,DQw9 was made by hybridizing MspI digested DNA with the DQA probe.2’
Taql Hi% -B RFLP analysis HLA-B RFLPG were used to distinguish the haplotypes in families where either one or both of the parents were DR-DQ homozygous or identical heterozygous. HLA-B RFLP analysis was done as described in ref. 23.
Table 1. Distribution (%) of DR-DQ phenotypes in patients with pulmonary India. DR
tuberculosis
DQ
compared
to healthy controls from South
DQBl*
DQAI”
Tuberculosis (n=38)
Controls (n=36)
I
w5
0501
0101
3
0
w15 w15 w15 w15 w15 w15 w15
w5 w5 w5 w6 w6 w6 w6
0501 0501 0501 0602 0602 0601 0601
0101 0102 0103 0102 0103 0102 0103
3 3 3 8 8
0 3 6 8 6 8 39
~16
w5
0502
0102
0
3
w17
w2
0201
0501
13
11
4 4
w8 W7
0302 0301
0301 0301
21 0
19 3
Wll
w7 w6
0301 0603
0501 0103
3 0
0 3
w13 w13
w6 w6
0604 0603
0102 0103
8 18
8 17
wll
1:
w14
w5
0503
0101
34
19
7 7
w2 w9
0201 0303
0201 0201
16 18
22 3
w8 W8
w4 WI
0402 0301
040 1 0601
0 0
3 3
9
w9
0303
0301
3
0
WlO
w5
0501
0101
II
3
*DQAI and DQBl alleles, in genomic nomenclature (1), were inferred from Taql DRB-DQA-DQB RPLP data. The correlation between assigning DQAl and DQBI alleles by PCR-SSO typing and indirectly from Taql DRB-DQA-DQB haplotypes was determined in 45 healthy South Indians and was found to be 100% (29).
HLA-DR and -DQ in pulmonary
Table 3. Sharing of HLA haplotypes between diseased and healthy siblings in 9 families with one parent and one offspring affected with pulmonary tuberculosis. Unaffected sibling sharing affected haplotype inherited from Affected parent Unaffected parent Family no. 1. 2. 4. 5. 6. I. 8. IO. 12. Total
1 haplotype shared
1
No haplotype shared
1 haplotype shared
No haplotype shared
3 4 1 1
I
2 3 1 1 4 1 2 I 1
1 2 0 2
0 1 1 1 3 1 1 2 0
9
16
15
10
2
I I 0 1
1 I
I
more frequent in Indonesian patients.15 However, the association was not significant after correction for the number of alleles tested. DR2 was also found increased in smear-positive pulmonary tuberculosis patients from South India.14 No association has been found with HLADR2 in other ethnic groups.6,‘3,‘7,‘8 Thus, the presumed and often cited DR2 association in tuberculosis is not convincing and has not been confirmed in subsequent studies in several different ethnic groups. In our study, we found an insignificant increase of the DR7,DQw9 haplotype in the patients when compared to the controls. DRwlS,DQw6, with the DQAl allele 0103 was more frequent in the controls than among the patients, but the difference was not statistically significant when the probability value was corrected for the number of comparisons made. Similarly in studies on North Indians,13 Egyptians6 and Americans,i’ no association with DR2 was found. HLA-DRw6 was found to be insignificantly underrepresented in North IndiansI with pulmonary tuberculosis. No DRw6 association, divided into DRw 13 and DRw 14, was observed in our patients, which is in agreement with the findings in Indonesians.15
tuberculosis
The analysis of haplotype sharing in the 9 families studied showed no association with the haplotypes inherited from affected or unaffected parents. This finding concurs with the study in Hong Kong Chinese I7 and did not confirm the finding of increased sharing of HLA haplotypes with affected siblings rather than unaffected ones as reported in ref.16. Furthermore no preferential sharing of DR2 was observed in contrast to the finding in North Indians.25 In conclusion, in South Indian patients with pulmonary tuberculosis, we found no association or linkage of disease susceptibility with the HLA class II region. Genetic factors have been shown to play an important role in determining the susceptibility to tuberculosis in animal? and early experiments have also shown that the genetic factors controlling resistance to tuberculosis are multiple and increasing. 27Recent studies have shown that the innate resistance and susceptibility to infection in different strains of mice infected with mycobacteria could be related to the Beg’ genes,=* which are located outside MHC on mouse chromosome 1.
Acknowledgements We sincerely acknowledge the staff members of the Clinic and Social work department of the Tuberculosis Research Centre, Madras, India, for their kind cooperation in the study. We are grateful to Prof. Ema Moller, Department of Clinical Immunology, Huddinge, Sweden for her valuable comments. The part of the work that was carried out in Sweden was supported by grants from the Karolinska Institute and Swedish Medical Research Council (Grant no. 00793).
References 1. Bodmer J G, Marsh SGE, Albert E et al. Nomenclature for factors of the HLA system 1990. Tissue Antigens 1991; 37: 97-104. 2. Dannenberg AM Jr. Delayed-type hypersensitivity and cellmediated immunity in the pathogenesis of tuberculosis. Immunol today 1991; 12: 228-233. 3. Al-Arif L I, Goldstein R A, Afronti L F, Janicki B W. HLA-Bl5 and tuberculosis in a North American black population. Am Rev Respir Dis 1979; 120: 1257-1278. 4. Xu Xingpei, Li Senbin, Wang Chaoying. Li Quanhui. Study on
Table 4. Summary of HLA-DR2 results in studies of patients with pulmonary tuberculosis
in different ethnic groups.
No. of patients
No. of controls
Ethnic
Typing method
Finding
uncorrected
P value corrected
Reference
group
P value
124
109
North Indians
Serology
No association
NS
NS
13
256
100
Hong Kong Chinese
Serology
No association
NS
NS
17
101
64
Indonesians
Serology
Positive association
co.01
NS
15
45
41
Black Americans
Serology
No association
NS
NS
18
42
43
Egyptians
Serology
No association
NS
NS
143
283
South Indians
Serology
Positive association
and Lung disease (1992) 73.280-284
No association or linkage with HLA-DR or -DQ genes in South Indians with pulmonary tuberculosis C. B. Sanjeevi*,
P. R. Narayanan t, R. Prabakart,
N. Charles?, B. E. Thomas?,
R. Balasubramaniamt,
0.Olerup*
Venterfor BioTechnology and Department of Clinical Immunology, Karolinska Institute, Huddinge, Sweden, and tTuberculosis Research Center, Indian Council of Medical Research, Madras, India S UMMA R Y. Studies of the HLA class II genes were performed in patients and multiple families with pulmonary tuberculosis from South India to seek any association of disease susceptibility with an individual allele or haplotype. TaqI RFLP analysis of HLA-DRB, -DQA and -DQB genes was done in 38 patients and 36 healthy control subjects. No significant association with any particular allele or haplotype was obtained. Linkage analysis performed in 12 families and haplotype sharing analysis in 9 families showed that the genetic susceptibility to pulmonary tuberculosis was not linked to the HLA region. The results suggest that the RFLP patterns of HLA class II genes DRB, DQA and DQB are not associated with susceptibility to pulmonary tuberculosis and that the genes controlling susceptibility or resistance may be located outside the HLA region. R&S U MI?. Des etudes de genes HLA classe II ont CtCentreprises chez des malades et des familles multiples
atteints de tuberculose pulmonaire en Inde du Sud, afin de chercher l’association d’une susceptibilite a la maladie avec l’existence d’allele ou d’haplotype individuels. Une analyse TaqI RFLP des genes HLA-DRB, -DQA, -DQB a CtCfaite chez 38 malades et 36 sujets temoins sains. Aucune association significative n’a CtC objectivee avec un allele ou haplotype en particulier. Une analyse de liaison entreprise dans 12 familles et une analyse de partage des haplotypes dans 9 familles ont montre que la susceptibilite genetique a la tuberculose n’etait pas like a la region HLA. Les resultats suggerent que les dispositions RFLP des genes HLA classe II, DRB, DQA et DQB ne sont pas associees a une susceptibilite a la tuberculose pulmonaire et que les genes qui controlent la susceptibilite ou la resistance doivent Ctrelocalises en dehors de la region HLA. R ES UM E N . Se realizaron estudios de genes HLA clase II en pacientes y familias con tuberculosis pulmonar
de1 Sur de la India, para buscar una asociacion de la susceptibilidad a la enfermedad con un alelo o haplotipo individual. Se realiz6 un analisis TuqI RFLP de 10s genes HLA-DRB, -DQA, -DQB en 38 pacientes y 36 controles sanos. No se obtuvo asociacion significativa con ningun alelo o haplotipo en particular. Un anilisis de ligazdn efectuado en 12 familias y un analisis de repartici6n de 10s haplotipos en 9 familias mostraron que la susceptibilidad genetica a la tuberculosis pulmonar no esti ligada a la region HLA. Los resultados sugieren que la disposici6n RFLP de 10s genes HLA clase II, DRB, DQA y DQB no estri asociada con la susceptibilidad a la tuberculosis pulmonar y que 10s genes que controlan la susceptibilidad o la resistencia podrian estar localizados fuera de la regi6n HLA.
Most genes of the major histocompatibility complex (MHC) are characterized by a high degree of allelic polymorphism. This has been determined using multiple techniques including serology, biochemical analysis, restriction fragment length polymorphism (RFLP) analysis and nucleotide sequence comparisons. Thus for the human MHC class II genes, 44 alleles of the DRBl gene, 15 of the DQBI gene and nine of the DQAl gene are currently recognized.’
The major function of the MHC molecules is to act as recognition elements for T lymphocytes, who have an obligatory requirement to co-recognize antigenic peptides with self-MHC products. Therefore, the MHC alleles inherited by an individual are one of the major determinants of the immune response phenotype. Soon after reliable techniques for the definition of human MHC alleles became available, it was noted that several diseases with a suspected immune pathogenesis were associated with human leucocyte antigens (HLA). The number of such associations rapidly increased and most of these have turned out to be associations with MHC
Correspondence to: C. B. Sanjeevi, Department of Endocrinology, Karolinska Hospital, S-104 01 Stockholm, Sweden. 280
HLA-DR and -DQ in pulmonary
class II alleles. Furthermore, the identification of nonHLA genes within the MHC and the phenomenon of linkage disequilibrium raise the possibility that a neighbouring gene of HLA or non-HLA status in linkage with the observed associated allele may be the true susceptibility gene. Tuberculosis is an infectious disease with a strong immunological basis, involving cell-mediated immunity.’ Since all T cell responses are MHC-dependent, the possible association between HLA class I and class II alleles, serologically defined, has been investigated in several studies in patients with tuberculosis. Previous studies on HLA class I alleles in patients with tuberculosis have shown positive association with B15 in American blacks,’ B15 and Bw35 in Chinese,4,5 A2 and B5 in Egyptians6 and with B8 in Canadians.’ The frequency of B 12 has decreased in Korean patients with tuberculosis.* Studies in pulmonary tuberculosis patients in European Caucasians,’ Japanese,” Mexican Americans,” South IndiansI and North Indians13 have not shown any significant correlation with the disease. Association with the HLA class II allele, DR2r4 and the linked specificity DQw 1, have been shown in patients with pulmonary tuberculosis.‘5 Insignificant increases of the occurrence of the DR2 allele have also been observed in several other ethnic group~.‘~,‘~ However, in studies on Hong Kong Chinese,” Egyptians6 no HLA-DR2 association was and black Americans,” found. The aims of the present study were two-fold, to assess association of HLA class II alleles (DR and DQ) with pulmonary tuberculosis utilizing genomic typing techniques and to perform linkage analysis in families with one parent and one child with the disease.
MATERIALS AND METHODS Subjects Patients attending the clinic of the Tuberculosis Research Centre, Madras, formed the study group. 38 unrelated patients with pulmonary tuberculosis, diagnosed on the basis of clinical, bacteriologic and radiographic evidence, were included in the study. 36 unrelated healthy volunteers, who formed the control group, were screened for tuberculosis and found negative. 12 nuclear families, in whom one of the parents and one child had the disease, were chosen for segregation analysis. Three of the 12 families were not included in the analysis of haplotype-sharing, as one of the parents was HLA class I and class II homozygous in 2 families and in a third family both parents were identical heterozygotes.
Southern blot analysis DNA was isolated from the peripheral
blood leukocytes
281
tuberculosis
using standard techniques. The isolated DNA was subjected to restriction enzyme digestions (TuqI and MspI), agarose gel electrophoresis, capillary blotting to nylon membrane, hybridization, stringency washes and autoradiography.”
TuqI DRB, DQA and DQB RFLP typing DR and DQ typing was performed by hybridizing Taql cleaved DNA with DRB, DQA and DQB cDNA probes.19 Restriction fragment patterns were analysed as previously described.“x2’ The nomenclature used is that of the serologically defined DR and DQ specificities associated with different allelic TaqI DRB-DQA-D&B haplotypes. The distinction between DR7,DQw9 and DR9,DQw9 was made by hybridizing MspI digested DNA with the DQA probe.2’
Taql Hi% -B RFLP analysis HLA-B RFLPG were used to distinguish the haplotypes in families where either one or both of the parents were DR-DQ homozygous or identical heterozygous. HLA-B RFLP analysis was done as described in ref. 23.
Table 1. Distribution (%) of DR-DQ phenotypes in patients with pulmonary India. DR
tuberculosis
DQ
compared
to healthy controls from South
DQBl*
DQAI”
Tuberculosis (n=38)
Controls (n=36)
I
w5
0501
0101
3
0
w15 w15 w15 w15 w15 w15 w15
w5 w5 w5 w6 w6 w6 w6
0501 0501 0501 0602 0602 0601 0601
0101 0102 0103 0102 0103 0102 0103
3 3 3 8 8
0 3 6 8 6 8 39
~16
w5
0502
0102
0
3
w17
w2
0201
0501
13
11
4 4
w8 W7
0302 0301
0301 0301
21 0
19 3
Wll
w7 w6
0301 0603
0501 0103
3 0
0 3
w13 w13
w6 w6
0604 0603
0102 0103
8 18
8 17
wll
1:
w14
w5
0503
0101
34
19
7 7
w2 w9
0201 0303
0201 0201
16 18
22 3
w8 W8
w4 WI
0402 0301
040 1 0601
0 0
3 3
9
w9
0303
0301
3
0
WlO
w5
0501
0101
II
3
*DQAI and DQBl alleles, in genomic nomenclature (1), were inferred from Taql DRB-DQA-DQB RPLP data. The correlation between assigning DQAl and DQBI alleles by PCR-SSO typing and indirectly from Taql DRB-DQA-DQB haplotypes was determined in 45 healthy South Indians and was found to be 100% (29).
HLA-DR and -DQ in pulmonary
Table 3. Sharing of HLA haplotypes between diseased and healthy siblings in 9 families with one parent and one offspring affected with pulmonary tuberculosis. Unaffected sibling sharing affected haplotype inherited from Affected parent Unaffected parent Family no. 1. 2. 4. 5. 6. I. 8. IO. 12. Total
1 haplotype shared
1
No haplotype shared
1 haplotype shared
No haplotype shared
3 4 1 1
I
2 3 1 1 4 1 2 I 1
1 2 0 2
0 1 1 1 3 1 1 2 0
9
16
15
10
2
I I 0 1
1 I
I
more frequent in Indonesian patients.15 However, the association was not significant after correction for the number of alleles tested. DR2 was also found increased in smear-positive pulmonary tuberculosis patients from South India.14 No association has been found with HLADR2 in other ethnic groups.6,‘3,‘7,‘8 Thus, the presumed and often cited DR2 association in tuberculosis is not convincing and has not been confirmed in subsequent studies in several different ethnic groups. In our study, we found an insignificant increase of the DR7,DQw9 haplotype in the patients when compared to the controls. DRwlS,DQw6, with the DQAl allele 0103 was more frequent in the controls than among the patients, but the difference was not statistically significant when the probability value was corrected for the number of comparisons made. Similarly in studies on North Indians,13 Egyptians6 and Americans,i’ no association with DR2 was found. HLA-DRw6 was found to be insignificantly underrepresented in North IndiansI with pulmonary tuberculosis. No DRw6 association, divided into DRw 13 and DRw 14, was observed in our patients, which is in agreement with the findings in Indonesians.15
tuberculosis
The analysis of haplotype sharing in the 9 families studied showed no association with the haplotypes inherited from affected or unaffected parents. This finding concurs with the study in Hong Kong Chinese I7 and did not confirm the finding of increased sharing of HLA haplotypes with affected siblings rather than unaffected ones as reported in ref.16. Furthermore no preferential sharing of DR2 was observed in contrast to the finding in North Indians.25 In conclusion, in South Indian patients with pulmonary tuberculosis, we found no association or linkage of disease susceptibility with the HLA class II region. Genetic factors have been shown to play an important role in determining the susceptibility to tuberculosis in animal? and early experiments have also shown that the genetic factors controlling resistance to tuberculosis are multiple and increasing. 27Recent studies have shown that the innate resistance and susceptibility to infection in different strains of mice infected with mycobacteria could be related to the Beg’ genes,=* which are located outside MHC on mouse chromosome 1.
Acknowledgements We sincerely acknowledge the staff members of the Clinic and Social work department of the Tuberculosis Research Centre, Madras, India, for their kind cooperation in the study. We are grateful to Prof. Ema Moller, Department of Clinical Immunology, Huddinge, Sweden for her valuable comments. The part of the work that was carried out in Sweden was supported by grants from the Karolinska Institute and Swedish Medical Research Council (Grant no. 00793).
References 1. Bodmer J G, Marsh SGE, Albert E et al. Nomenclature for factors of the HLA system 1990. Tissue Antigens 1991; 37: 97-104. 2. Dannenberg AM Jr. Delayed-type hypersensitivity and cellmediated immunity in the pathogenesis of tuberculosis. Immunol today 1991; 12: 228-233. 3. Al-Arif L I, Goldstein R A, Afronti L F, Janicki B W. HLA-Bl5 and tuberculosis in a North American black population. Am Rev Respir Dis 1979; 120: 1257-1278. 4. Xu Xingpei, Li Senbin, Wang Chaoying. Li Quanhui. Study on
Table 4. Summary of HLA-DR2 results in studies of patients with pulmonary tuberculosis
in different ethnic groups.
No. of patients
No. of controls
Ethnic
Typing method
Finding
uncorrected
P value corrected
Reference
group
P value
124
109
North Indians
Serology
No association
NS
NS
13
256
100
Hong Kong Chinese
Serology
No association
NS
NS
17
101
64
Indonesians
Serology
Positive association
co.01
NS
15
45
41
Black Americans
Serology
No association
NS
NS
18
42
43
Egyptians
Serology
No association
NS
NS
143
283
South Indians
Serology
Positive association
