Immune Netw.  2002 Dec;2(4):242-247. 10.4110/in.2002.2.4.242.

Polymorphisms in the TNF-alpha Gene and Extended HLA and TNF-alpha Haplotypes in Koreans

• Park YJ
• Park HJ
• Park MH

• KMID: 1974524
• DOI: http://doi.org/10.4110/in.2002.2.4.242

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.

Keyword

TNF-alpha; HLA; polymorphism; single nucleotide polymorphism (SNP); haplotype; Korean

MeSH Terms

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*
HLA-A Antigens
Tumor Necrosis Factor-alpha