HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.

High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program.

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

[Study on HLA-DRB1 alleles in patients with familial hepatitis B in Shanxi].

OBJECTIVE: To study the association between HLA-DRB1 alleles and familial hepatitis B. METHODS: HLA-DRB1 alleles of 151 people in the familial hepatitis B families were detected,by using the the polymerase chain reaction-sequence specific oligonucleotide probing (PCR-SSOP) technique. RESULTS: The allele frequency of HLA-DRB1 * 0701 in the chronic hepatitis B (CHB) group was markedly higher than that in the normal control group (17.8% vs 7.4%), with significant correlation between them (P < 0.05, A = 1/0.367 approximately 2.725). The allele frequencies of HLA-DRB1 * 0401/0403/0405 and HLA-DRB1 * 1301/1302 in the normal control group (16.2%, 4.4% ) were markedly higher than that in the CHB group (5.1%, 0), with statistical significance (P < 0.05, A = 3.602; P < 0.05). The other alleles between the CHB group and the normal control group are no significant differences. CONCLUSION: HLA-DRB1 * 0701 is closely associated with the susceptibility to familial hepatitis B,and may be the susceptible or linkage gene. HLA-DRB1* 0401/0403/0405 and HLA-DRB1 * 1301/1302,in inverse proportion to the susceptibility to familial hepatitis B, may be the resistant gene. They may regulate the outcome of familial HBV infection in a patient.

[Polymorphism of HLA-A,-B and DRB1 in Han population of Shanxi province].

OBJECTIVE: To investigate the polymorphism of HLA-A, -B, -DRB1 genes in Han population in Shanxi of China. METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify the polymorphism of HLA-A, -B, -DRB1 genes of 7440 healthy and unrelated individuals of Han population in Shanxi, and the gene frequency distribution of HLA-A, -B, -DRB1 genes in population was compared with the results from other populations. RESULTS: Eighteen HLA-A, forty HLA-B and thirteen HLA-DRB1 alleles were found. The frequencies of A*02, A*24, A*11, A*01, A*03, B*13, B*51, B*15, B*40, B*35, DRB1*15, DR*09, DR*12, DR*04, DR*07 alleles in Hans of Shanxi were significantly higher and displayed distinctive distribution profiles when compared with those of Caucasian and Afro-American. CONCLUSION: The HLA-A,-B,-DRB1 distribution in Shanxi Han population shares some genetic characteristics with other Han populations in northern part of China, but it exhibits its own characteristics.