MICA GENE POLYMORPHISM AND THE RISK TO DEVELOP CERVICAL INTRAEPITHELIAL NEOPLASIA.
C.B. Sanjeevi, M. Ghaderi, P. Hjelmström, G. Hallmans, F.Wiklund, P. Lenner, J. Dillner. Department of Molecular Medicine, Karolinska Hospital, Microbiology and Tumor Biology Centrum, Karolinska Institute, Stockholm, Department of Nutritional Research, University of Umeå, Umeå, Sweden; 

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Cervical intraepithelial neoplasia (CIN) is known to be associated with HPV infection and DR15-DQ6 (DQB1*0602). The aim of the study was to analyze the association of MICA microsatellite alleles in CIN patients and controls, HPV seropositive and negative patients and DQ6 positive and negative patients from the Vasterbotten County in Northern Sweden. MICA gene is located in the HLA class III region and is expressed in keratinocytes, monocytes and endothelial cells. Sequence determination of MICA gene identifies trinucleotide repeat (GCT) microsatellite polymorphism. Five alleles are identified 4, 5, 6 and 9 repetitions of GCT and 5 repetitions of GCT with 1 additional nucleotide insertion (GGCT) and are referred to as A4, A5, A5.1, A6 and A9. MICA was typed by PCR-microsatellite typing. HLA genotyping for DQ was done by PCR-SSO in 74 patients and 153 matched unrelated controls. ELISA using capsid protein as antigen identified HPV16 and 18 antibodies. All 9/9 (100%) HPV18 seropositive patients carried allele 5 compared to 35/65 (53%) HPV18 seronegative patients (Odds ratio 16.3; p<0.05). Of these 9 HPV18 seropositive and MICA 5.1 positive patients 7 were diagnosed with CIN3. None of the alleles of MICA was positively or negative associated in all CIN patients. Similarly no association was observed in HPV16 seropositive compared to seronegative patients and DQ6 positive patients compared to DQ6 negative patients. Our findings suggest that MICA may be important in the etiopathogenesis of CIN.