Polymorphisms in the TNF-alpha Gene and Extended HLA and TNF-alpha Haplotypes in Koreans.
- Author:
Yoon June PARK
1
;
Hye Jin PARK
;
Myoung Hee PARK
Author Information
- Publication Type:Original Article
- Keywords: TNF-alpha; HLA; polymorphism; single nucleotide polymorphism (SNP); haplotype; Korean
- MeSH: Alleles; Apoptosis; Asian Continental Ancestry Group; Autoimmune Diseases; Autoimmunity; Gene Frequency; Haplotypes*; HLA-A Antigens; Humans; Inflammation; Insulin Resistance; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Tumor Necrosis Factor-alpha*
- From:Immune Network 2002;2(4):242-247
- CountryRepublic of Korea
- Language:Korean
- Abstract: BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known to play an important role in various conditions such as inflammation, autoimmunity, apoptosis, insulin resistance and sleep induction. Five single nucleotide polymorphisms (SNPs) have been known to affect the transcriptional activities of TNF-alpha: 1,-031T/C, -863C/A, -857C/T, -308G/A and -238G/A. METHODS: We have investigated 5 SNPs of the promoter region of TNF-alpha gene, the distribution of 5-locus TNF-alpha haplotypes, and their haplotypic associations with previously typed HLA-A, -B and -DRB1 loci in 107 healthy unrelated Koreans. TNF-alpha SNPs were typed using PCR-single-strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. RESULTS: The allele frequencies of -1,031C, -863A, -857T, -308A, and -238A, which are known as the high-producer-type, were 19.3%, 15.9%, 14.0%, 5.9%, and 2.9%, respectively. The frequency of -308A allele, known to be associated with autoimmune diseases, was 5.9% in Koreans which was lower than Caucasians (14-17%) and somewhat higher than Japanese (1.7%). Five most common TNF-alpha haplotypes (-1,031/ -863/ -857/ -308/ -238) comprised over 95% of total haplotypes: TCCGG (58.4%), CACGG (14.8%), TCTGG (13.7%), TCCAG (5.3%), and CCCGA (3.1%). Strong positive associations (P<0.001) were observed between TCCGG and B62; between CACGG and B51, DRB1*0901; between TCTGG and B35, B54, B59, DRB1* 1201; and between TCCAG and A33, B58, DRB1*0301, DRB1*1302. Five most common extended haplotypes (>3%) comprised around 16% of total haplotypes: A33-B58- TCCAG-DRB1*1302, A24-B52-TCCGG-DRB1*1502, A33-B44-TCCGG-DRB1*1302, A24- B7-TCCGG-DRB1*0101, and A11-B62-TCCGG-DRB1*0406. The distribution of extended HLA and TNF-alpha haplotypes showed that most of HLA haplotypes were almost exclusively associated with particular TNF-alpha haplotypes. CONCLUSION: The results obtained in this study would be useful as basic data for anthropologic studies and disease association studies in Koreans.
