Abstract
Polymorphisms of the 5'-flanking promoter/enhancer region of the TNAFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5'-flanking region of the TNFA gene from -1107 to 66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position 1031, -863, -857, -307 and -237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of the TNFB gene as well as HLA-DR9. The genotype at 1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA-B.
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