Impact Of ICAM-1Gene K469E, K56M Polymorphisms On Plasma SICAM-1Levels In Yugur, Tibetan And Han Nationalities

Objective:This study was purposed to investigate ICAM-1gene K469E (A/G,rs5498) and K56M (A/T,rs5491) polymorphisms and sICAM-1plasma levels in Yugur, Tibetan and Han nationalities, then to analyze comparatively genotypes and allele frequencies distribution in different ethnic groups, and explore whether there was association between ICAM-1SNPs and sICAM-1levels in plasma.Methods:We collected EDTA-anticoagulant venous blood from Yugur (327cases), Tibetan (400cases) and Han (126cases) people, utilized the whole blood genomic DNA extraction kits to extract DNA, then, DNA SNPs were analyzed by PCR-RFLP, genotype was judged by gel scan imaging system after agarose gel electrophoresis, the gene sequence was determined and the distribution of ICAM-1genotypes and allele frequencies were compared from different ethnic groups, besides, group representativeness was tested via the Hardy-Weinberg genetic equilibrium. Finally, we detected the human sICAM-1plasma levels using human ICAM-1ELISA kits.Results:DNA sequencing result was consistent with PCR-RFLP analysis. In three nationalities, we detected the KK, KE and EE three genotypes at ICAM-1K469E gene locus, the genotype distribution was not statistically significantly different, while the K, E allele frequency distribution was statistically significantly different (P<0.05). Both of genotype and allele frequency distribution between Yugur, Tibetan respectively and Han nationalities were statistically significantly different (P<0.05). The sICAM-1plasma levels at ICAM-1K469E allele locus in K individuals (253.409±122.547,185.061±97.063μg/L) were higher than non-K allele (145.151±110.961μg/L), the three genotypes were significantly different (P<0.01). K56M site had KK, KM two genotypes, the MM genotype was not detected in three ethnic groups; the difference of two genotypes and K, M allele frequencies between Yugur and Han population was statistically significantly different (P<0.05). The sICAM-1plasma level of ICAM-1K56M site with KK genotype (253.409±122.547μg/L) was higher than that with KM genotype (168.350±103.630μg/L), the difference was statistically significant (P<0.01). Among three ethnic groups, K469E and K56M genotypes and allele frequencies distribution of ICAM-1gene were in accord with Hardy-Weinberg genetic equilibrium (P>0.05). In Yugur and Tibetan groups, sICAM-1plasma levels (224.418±80.950,214.298±111.508μg/L) were higher than that in Han group (175.063±125.266μg/L), the difference among the three ethnic groups was statistically significant (P<0.05), pairwise comparisons indicated that sICAM-1plasma levels between Yugur and Han group were statistically significantly different (P<0.01), that was significantly different between Tibetan and Han group (P<0.05).Conclusion:It was concluded that in Yugur, Tibetan and Han nationalities, the genotypes and gene frequencies of two polymorphism sites K469E and K56M in ICAM-1were KK/KE-type, KK-type and K allele, moreover, the ratio of them in Yugur and Tibetan group was higher than that in Han, ICAM-1genotype and allele frequency distribution in this study had ethnic representativeness. ICAM-1gene K469E and K56M polymorphisms were likely to affect the sICAM-1plasma level and were susceptible factors of some diseases at different altitudes and different ethnic groups. K469E K allele may be a genetic risk factor, while K56M M allele a genetic protective factor for some plateau related diseases.