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Summary Syphilis is a sexually transmitted infection caused by the Treponema pallidum subspecies pallidum spirochaete bacterium. The killer immunoglobulin-like receptor (KIR) gene family encodes cell surface receptors that are found on natural killer (NK) cells and certain T-cell subsets. NK cells are fast-acting effector lymphocytes of innate immunity that respond to infection. The activity of NK cells depends on the dynamic balance of activating and inhibitory signals that are transmitted through respective receptors including KIRs. KIR2DS4 is the only activating KIR gene in KIR haplotype A. KIR1D is a partial deletion KIR2DS4 variant encoding protein devoid of transmembrane region. Up to now, there is no knowledge of association of KIR2DS4 and its variant KIR1D with syphilis in a population that belongs to KIR gene haplotype A. Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype KIR genes in 190 patients with syphilis and 192 healthy controls. The gene frequencies of KIR2DS4 and KIR1D were analysed for the association with syphilis in patients and healthy controls who belong to KIR gene haplotype A. The gene frequency of KIR1D/ KIR1D in patients with syphilis classified as haplotype A was 16.85% and was significantly higher than that in the control group (6.59%) ( P = 0.032). However, there was no significant difference for the gene frequencies of KIR2DS4/ KIR2DS4 and KIR2DS4/ KIR1D between the two groups ( P > 0.05). KIR1D/ KIR1D was found in association with susceptibility to syphilis in the Chinese Han population that belongs to KIR gene haplotype A. [ABSTRACT FROM AUTHOR]