APOL1 Gene Mutation Screening In Patients With HIV Infection And Kidney Diseases

Objective:APOL1 gene variants(especially G1 and G2 risk alleles)are one of the most important causes for the genetic susceptibility to renal damage in African Americans with human immunodeficiency virus(HIV)infection.However,we did not find these two variants in patients with end stage renal disease in our country,and it is unclear whether there were other variants of APOL1 in Chinese patients with HIV infection and kidney diseases.In this study,APOL1 gene mutations were screened in patients who had HIV infection and kidney injuries in our country.Methods:We summarized the clinical features of six patients suffering from kidney diseases and HIV infection.Primers for APOL1 gene exons and regulatory region were designed.Peripheral blood was collected and genomic DNA was extracted.PCR amplification was performed,and the amplified products were identified by agarose gel electrophoresis.Finally,the regulatory and coding region of APOL1 gene were sequenced.The frequencies of the mutant alleles were compared among the 6 HIV-infected patients with kidney disease,4 HIV-infected patients without kidney disease,60 matched normal controls,as well as 1000 Genomes Project data.Results:All the 6 cases presented with different degrees of microscopic hematuria,proteinuria,serum albumin reduction;as well as increased serum creatinine level in two patients;dyslipidemia in two cases.One patient had a concomitant hepatitis B virus infection,another patient had a concomitant hepatitis C virus infection.Heterozygous mutation in regulatory region,A-565 G,was found in 1 case.Five mutations in coding region were found in all 6 cases,consist of three missense mutation:G496A(Glu166Lys),G732A(Met244Lle),G812A(Arg271Lys),and two synonymous mutation:C702A,G1008 A.All of the variants were also found in the 4 HIV-infected patients without kidney disease,60 matched normal controls,as well as 1000 Genomes Project data.Except for some differences with African American individuals,there were no remarkable significant differences of the frequencies of these variants among these patients,controls and data from 1000 Genome Project.Conclusion:In this study,10 patients with HIV infection,renal damage in 6 cases,of which 2 cases the serum creatinine have been elevated,suggesting that HIV infection may lead to poor prognosis of the kidney.There was no APOL1 G1/G2 mutation identified in the HIVAN,and there was no other special variation of APOL1 gene in these patients.It suggested that there could be other risk factors for HIVAN in our country.