Functional Study of ELMO-1 Genetic Variant in Diabetes Mellitus Type II and Diabetic Nephropathy

Introduction: Engulfment and Cell Motility (ELMO-1) genetic variation was strong candidate of genetic risk for diabetic nephropathy (DN). Several previous study reported genetic variation in intron of ELMO-1 gene as DN risk factor but the study reported genetic variation in promoter of this gene still limited. Genetic variation in promoter of gene promises as diseases risk factor, that may correlate with the functional of genetic variant, whereas difference genotype has difference protein level. Aims: This study was functional genetic variant study which revealed functional of three ELMO-1 genetic variation in promoter. The difference of protein ELMO-1 protein level between genotype was investigated. Methods: Study design was cross sectional. Totally 74 patients with DM type II which full filled study criteria was participated, as much 43 patients have DN. We investigated 3 genetic variation in ELMO-1 promoter with Sanger sequencing. The genetic variants were ELMO-1 rs1882071 G/T, rs13242914 C/T, rs13242348 A/G. Blood ELMO-1 was measure with Enzyme-linked Immunosorbent Assay (ELISA). Result: Subject who suffered DM type II with GG genotype of rs1882071 has higher mean ELMO-1 blood level than GT and TT genotype (p value 0.735). Subject with TT genotype of rs13242914 has higher mean ELMO-1 blood level than CT and CC genotype (p value 0.511). Subject with GG genotype of rs13242348 has higher mean ELMO-1 blood level than AG and AA genotype (p value 0.634). Similar trends also shown in subject who suffered diabetic nephropathy as renal complication of DM type II with p value (0.846; 0.230; 0.847) respectively for rs1882071 G/T, rs13242914 C/T, rs13242348 A/G. Conclusion: Blood protein ELMO-1 level was difference between genotype in subject who suffered DM type II or with DN complication. None of them was statistically significant, it may cause by other genetic variation or other factor that may influence blood ELMO-1 level.