Possible protective role of HLA-B*2706 for ankylosing spondylitis.

HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.

Influence of gender and age at onset on the HLA associations in Chinese with insulin-dependent diabetes mellitus.

IDDM in Singaporean Chinese was associated with HLA B58, DRB1*0301, DQB1*0201, and joint occurrences of DRB1*0301/*0901 and DRB1*0301/*04. Of the DR4s the frequencies of DRB1*0401, *0404, and *0405 were higher and *0406 was lower in patients compared to controls. DRB1*0301/*0901 was observed mainly in female patients and the frequency showed an inverse relationship with age at onset, whereas DRB1*0301/*04 was observed mainly in male patients and also showed an inverse relationship with age at onset. DRB1*1202 showed an increasing frequency with age at onset. IDDM patients had a higher frequency of homozygous NAsp57 DQ beta chains and a lower frequency of homozygous Asp57 DQ beta chains compared to controls, especially in younger onset patients.

HLA class 2 genes in Singaporean Chinese rheumatoid arthritis.

This study analysed HLA class 1 and 2 allele associations in Singaporean Chinese patients with RA. Seventy patients (ARA definite or classical) and 80 controls were typed for HLA class 1 alleles by serology and class 2 alleles by serology and the PCR/SSO method. RA patients had higher frequencies of DRB1*0405 (40 vs 12.5%; corrected probability value (PC) < 0.02, relative risk (RR) = 4.7, 95% confidence limit (CL) 2.1-10.6), DRB1*1001 (14.3 vs 1.3%; PC = 0.06, RR = 13.2, 95% CL 1.6-105.7), DQB1*0401 (38.6 vs 12.5%; P = 0.006, RR = 4.4, 95% CL 1.9-10.0) and DQB1*0501 (20 vs 5%; PC = 0.048, RR = 4.8, 95% CL 1.5-15.2). It is concluded that Chinese RA is associated primarily with HLA DRB1*0405 and DRB1*1001 which share common amino acid sequences in the third hypervariable region of the DR beta chains shown to be associated with RA in other ethnic groups. Patients without DRB1*0405 and *1001 had a higher frequency of DRB1*0901, which is in linkage disequilibrium with HLA B46 in the Chinese.

Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves' disease.

Human Leucocyte Antigen (HLA) A, B, C, DR, DQ and DP locus alleles in 35 Chinese patients with Graves' disease and 80 controls were typed for using serological and DNA polymerase chain reaction/sequence specific oligonucleotide (PCR/SSO) methods. B46 was found to be strongly associated with male patients (p = 0.0002; RR = 8.2, 95% confidence interval 2.1-32.2). In HLA class 1 alleles, besides B46, the frequencies of A2 and Cw1 were increased and A24 and B63 decreased in patients compared to controls. In HLA class 2 alleles, the frequencies of DRB1*1602, *0301, *1405, DRB5*02, DQB1*0502 were increased and DRB1*1501, DQB1*0301 decreased in patients.

HLA and Singaporean Chinese myasthenia gravis.

Chinese Singaporean myasthenia gravis (MG) patients are associated with three HLA haplotypes: Cw1 B46 DRB1*0901 DQB1*0303 DQA1*03, DRB1*14 DRB3*0202 DQB1*0503 DQA1*0101 and DRB1*1202 DRB3*0301 DQB1*0301 DQA1*0601. The B46 haplotype was associated with the total group of MG patients but in particular with those with younger onset, low antiacetylcholine receptor (anti-AchR) titres, with only ocular lesions and with normal thymuses. The DRB1*14 haplotype was associated with thymic hyperplasia, younger onset patients, with high anti-AchR titres and with generalised MG. The DRB1*1202 haplotype was associated with thymoma, older onset patients, ocular lesions, and mid to high anti-AchR titres.

HLA in Singapore Chinese with rheumatoid arthritis.

The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease.

HLA Bw46 and DR9 associations in Graves' disease of Chinese patients are age- and sex-related.

The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46).

HLA and antibiotic allergic skin eruption.

Chinese patients with cutaneous eruption due to antibiotics were found to be positively associated with HLA-BW46 (RR = 2.5; 95% confidence limit 1.2-4.9) and negatively associated with HLA-B40 (RR = 0.46; 95% confidence limit 0.22-0.98). The association with HLA-BW46 was even higher in patients with ampicillin sensitivity (RR = 3.5; 95% confidence limit 1.4-9.0).

HLA-DR antigens in Chinese children with insulin-dependent diabetes mellitus.

We studied the distribution of HLA-DR and MT1, MT2, MT3 genotypes in 23 Chinese children with insulin-dependent diabetes mellitus (IDDM). The frequency of DR3 was 48% in IDDM children compared to 14% of normal controls (corrected p = 0.0098, RR = 5.70). The frequency of DR4 was not increased. These differences when compared with the results of Western populations may contribute to the relative rarity of IDDM among Chinese children.

HLA and Chinese patients with juvenile onset diabetes mellitus.

The HLA profile of 147 Chinese patients with juvenile onset diabetes mellitus was studied. There were HLA associations related to different age of onset of the disease. The patients who presented during the first decade of life had strong linkages with AW 33, B 17 and BW 22 (BW 54/55) but a weak association with DR 4. In contrast, patients whose age of onset ranged from 31 to 39 years had increased frequency of BW 46. Patients with diabetic complications (retinopathy, nephropathy, neuropathy and peripheral vascular disease) which were present singly or in combination were associated with HLA AW 33 and B 17. It would appear that genetic factor may be related to both the age of onset of diabetes as well as to the development of complications.

HLA and nasopharyngeal carcinoma in Malays.

HLA associations were observed in unrelated Malay patients with nasopharyngeal carcinoma (NPC). HLA-B18 was observed in 18/45 (40%) Malay NPC patients compared to 22/167 (13%) Malay normals (P = 0.0001; Pc = 0.0027, RR = 4.4). The frequency of HLA-B17, one of the antigens associated with Chinese NPC, was also increased among Malay NPC (13/45 29%) compared to controls (18/167 11%; P = 0.003, Pc = 0.07 RR = 3.4). Similar to the findings among Chinese NPC, the frequency of B17 was higher in early onset (less than or equal to 30 years) Malay NPC resulting in a higher relative risk (RR = 5.0).

HLA-system in Chinese children with insulin-dependent diabetes mellitus: a strong association with DR3.

We studied the distribution of HLA-A, B, and DR and MT1, MT2, MT3 genotypes in all 20 Chinese children with insulin-dependent diabetes mellitus (IDDM) attending the four government pediatric units in Singapore. We found an increase in HLA BW22 but the corrected probability value was not statistically significant. AW33 and B17 were observed in 50% and 55% of IDDM children, respectively, compared with 11% and 13% of normal controls, respectively. The values for AW33 were as follows: corrected P = 0.00094 and relative risk (RR) = 8.17; for B17 they were corrected P = 0.001 and RR = 7.55. In addition, the frequency of DR3 was 50% in IDDM children compared with 14% of normal controls (corrected P = 0.0019, RR = 6.20). AW33, B17, and DR3 are in linkage disequilibrium in our normal Chinese population. All ten patients who were positive for DR3 also had B17. The frequency of DR4 was not increased, and there were no protection IDDM related antigens found. These differences compared with the results in Western populations may contribute to the relative rarity of IDDM among Chinese children.

HLA and filariasis in Sri Lankans and Indians.

Similar HLA association was found in patients with elephantiasis in Sri Lankans and Southern Indians. HLA-B15 was observed in 13/44 (30%) Sri Lankan patients with elephantiasis compared to 1/27 (4%) Sri Lankan controls (p = .0058; RR = 10.9) and in 5/8 (28%) Southern Indian elephantiasis compared to 10/101 (10%) Southern Indian controls (p = 0.04; RR = 3.5). In combining the data, the significance of the difference of the frequency of B15 between patients with elephantiasis and controls was even more marked (p = 0.00045; corrected p = 0.012; RR = 4.4).

HLA and systemic lupus erythematosus in Chinese.

Seventy-five unrelated Chinese SLE patients were HLA typed and subdivided into mild and severe disease. The HLA-B13 was associated with mild disease. Fourteen of 30 (46.7%) mild disease patients had B13 compared to 63/330 (19.1%) normal subjects (p less than 0.0005, corrected p less than 0.013, RR = 3.7). The HLA-B17 on the other hand was observed in 29% of 45 severe disease patients compared to 13.9% of 330 normal subjects (p less than 0.01, RR = 2.5). The frequency of HLA-B17 in 11 patients who died was even higher (45.5%).

HLA and psoriasis in the Chinese.

The HLA locus A, B and C antigen frequency of 70 unrelated Chinese patients with psoriasis were compared to that of 330 normal subjects. The frequency of 1, Aw30 and B13 were significantly elevated among patients compared to normals, even after correction for the number of antigens typed for. The joint occurrence of Aw30, B13 was observed in 20/70 (37.1%) patients compared to 8/330 /2.4%) normals (chi 2 = 60.7, RR = 16.1). Aw30 and B13 were found to be in significant linkage disequilibrium in patients as well as normals.