SUN-453 Association study of mitochondrial genome with sepsis

Abstract

Sepsis is a clinical syndrome of high mortality and morbidity and still has a lot of controversy in mechanism. Mitochondria are the core part of the cell oxygen metabolism and mitochondrial dysfunction may have a profound impact on sepsis and multiple organ damage. Mitochondrial single nucleotide polymorphisms, in Europe and in the Han nationality have been shown to affect the prognosis of sepsis, however, similar to many complex diseases, the exact effect of mtDNA variation on sepsis and how to influence is not clear. With the development of genome sequencing technology and biological information, it is possible to use the next generation sequencing (NGS) to deal with that. To investigate the relationship between mitochondrial haplotypes and the prognosis of severe sepsis, and to screen the mitochondrial DNA single nucleotide polymorphisms associated with severe sepsis. Peripheral blood DNA from 151 sepsis patients and 103 healthy people were obtained. Mitochondrial genome wide association study of sepsis was conducted based on the mitochondrial DNA barcode sequencing method. We compared the mitochondrial haplotype distribution in the disease and control group, and the relationship between haplotype and prognosis of disease. Single nucleotide polymorphisms associated with disease onset and prognosis were screened. Association analysis based on the mitochondrial DNA sequencing found 9 loci associated with sepsis and controls: A (OR=0.2186, p=4.06E-05), B (OR=0.2271, p=0.001107), C (OR=0.2274, p=0.003112), D (OR=5.221, p=0.003419), E (OR=2.532, P=0.02615), F (OR=0.2478, p=0.02668), G (OR=0.2478, p=0.02668), H(OR=2.327, p=0.02913) and I (OR= 0.2256, p=0.03349). And 1 loci associated with in-hospital mortality of sepsis patients. J was associated with in-hospital mortality (OR=2.469, p=0.04966). There was no difference in the distribution of mitochondrial haplotypes among the groups. mitochondrial SNP A/B/C/D/E/F/G/H and I are associated with sepsis, while J is associated with the in-hospital deaths in sepsis patients.