Allele typing of human <i>TNFA</i> 5′‐flanking region using polymerase chain reaction‐preferential homoduplex formation assay (PCR‐PHFA): linkage disequilibrium with HLA class I and class II genes in Japanese

• M. Matsushita

• N. Tsuchiya

• T. Nakayama

• J. Ohashi

• T. Shibue

• M. Shiota

• T. Oka

• A. Yamane

• K. Tokunaga

抄録

Tumor necrosis factor α plays a substantial role in a number of conditions such as inflammation, autoimmunity, insulin resistance and sleep. Three new single nucleotide polymorphisms, −1,031 T/C, −863 C/A and −857 T/C, were recently identified in the upstream 5′‐flanking region of TNFA in the Japanese population. In the present study, we developed polymerase chain reaction (PCR)‐preferential homoduplex formation assay for the single‐step allele typing of TNFA , and determined the genotypes of 271 healthy unrelated Japanese individuals. Four haplotypes, −1,031/−863/−857 TCC, TCT, CAC and CCC, were found to constitute the majority, if not all, of the TNFA alleles of healthy Japanese population. These alleles were designated as TNFA‐U01, ‐U02, ‐U03 and ‐U04 , respectively, in the order of frequency. Based on HLA‐A, ‐B and ‐DRB1 genotypes together with TNFA genotypes, multi‐locus haplotypes were analyzed. Significant positive associations were observed between TNFA‐U01 and A*3303, B*5201, B*4403, B*4601, B*0702, DRB1*1502, DRB1*0101, DRB1*1302 , between TNFA‐U02 and B*5401, B*3501, DRB1*0405, DRB1*0407 , between TNFA‐U03 and B*4006, B*4002, DRB1*0803, DRB1*0802, DRB1*0403, DRB1*0901 , and between TNFA‐U04 and B*4801 . Four‐locus haplotype estimation revealed that A*3303‐B*4403‐TNFA‐U01‐DRB1*1302, A*2402‐B*5201‐TNFA‐U01‐DRB1*1502 and A*2402‐B*5401‐TNFA‐U02‐DRB1*0405 constitute major extended haplotypes in Japanese. Interestingly, TNFA alleles previously shown to have a higher promoter activity ( U02, U03 ) were found to form haplotypes with certain DRB1 alleles associated with T helper 1 (Th1)‐dominant diseases such as rheumatoid arthritis, insulin dependent diabetes mellitus and Crohn’s disease in Japanese. In contrast, TNFA allele with a low promoter activity ( U01 ) is in linkage disequilibrium with the DRB1 alleles associated with T helper 2 (Th2)‐dominant diseases such as atopic dermatitis and ulcerative colitis. These observations raise the possibility that TNFA upstream promoter region polymorphisms contribute to some of the HLA‐disease associations.

収録刊行物

• Tissue Antigens

  Tissue Antigens 54 (5), 478-484, 1999-11

  Wiley

キーワード

• Genetics
• Biochemistry
• Immunology
• General Medicine
• Immunology and Allergy

詳細情報

• CRID: 1362544419556777216
• NII論文ID: 30013461349
• DOI: 10.1034/j.1399-0039.1999.540505.x
• ISSN: 13990039
• ISSN: 00012815
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1034%2Fj.1399-0039.1999.540505.x
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1034/j.1399-0039.1999.540505.x
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