Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Apolipoprotein L1

The APOL1 gene encodes an apoplipoprotein that binds to apolipoprotein A1 and is common in hight density lipoprotein particles. It plays an important role in lipid metabolism. Genetic variations are associated with resistance to trypanosoma brucei infections and prediposition to FSGS type 4.

Epidemiology

Population

The two APOL1 variants G1 and G2 are common among Subsaharan Africans. The incidence there is 1:13-15. This hight frequency is explained by a protection against Trypanosoma infections. Interestingly the frequency in East Africa, in particular Ethiopia, with mere 5% is significantly lower though Trypanosoma infections are endemic there too. Among Caucasians and Asians the frequency is very low.[Error: Macro 'ref' doesn't exist]

Disease

Carrier of one oth the APOL1 variants G1 or G2 have a five fold increased risk of albuminuria. The anual decline in glomerular filtration rate is 0,45% faster.[Error: Macro 'ref' doesn't exist]

Aside of the two risk alleles G1 and G2 no other mutations are described in the APOL1 gene so far.

Interpretation

The G1 (NM_145343.2:[c.1072A>G,c.1200T>G]) and the G2 (NM_145343.2:c.1212_1217delTTATAA) alleles show a higher susceptibility to chronic kidney disease based on FSGS while at the same time these alleles seem protective against human African trypanosomiasis.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 20 days
Specimen type genomic DNA

Related Diseases:

Resistance to trypanosoma brucei
APOL1
Hereditary FSGS type 4
APOL1
Apolipoprotein deficiency
APOA5
APOB
APOC1
APOC2
APOC3
APOE
APOL1
APOM
Apolipoprotein A1 deficiency
APOA1
Apolipoprotein A2 deficiency
APOA2
Apolipoprotein F deficiency
APOF
Apolipoprotein H deficiency
APOH
CLU
Acute myeloid leukemia
JAK2

References:

1.

Ko WY et al. (2013) Identifying Darwinian Selection Acting on Different Human APOL1 Variants among Diverse African Populations.

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2.

Reidy KJ et al. (2018) Fetal-Not Maternal-APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry.

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3.

Duchateau PN et al. (2001) Apolipoprotein L gene family: tissue-specific expression, splicing, promoter regions; discovery of a new gene.

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4.

Page NM et al. (2001) The human apolipoprotein L gene cluster: identification, classification, and sites of distribution.

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5.

Mimmack ML et al. (2002) Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.

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6.

Monajemi H et al. (2002) The apolipoprotein L gene cluster has emerged recently in evolution and is expressed in human vascular tissue.

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7.

Vanhamme L et al. (2003) Apolipoprotein L-I is the trypanosome lytic factor of human serum.

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8.

Pérez-Morga D et al. (2005) Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes.

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9.

Genovese G et al. (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans.

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10.

Duchateau PN et al. (1997) Apolipoprotein L, a new human high density lipoprotein apolipoprotein expressed by the pancreas. Identification, cloning, characterization, and plasma distribution of apolipoprotein L.

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11.

Freedman BI et al. (2016) APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

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12.

Sampson MG et al. (2016) Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects.

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13.

Chen TK et al. (2016) The evolving science of apolipoprotein-L1 and kidney disease.

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14.

Ma L et al. (2016) APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease.

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15.

Gutiérrez OM et al. (2016) APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans.

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16.

Peralta CA et al. (2016) APOL1 Genotype and Race Differences in Incident Albuminuria and Renal Function Decline.

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17.

Tzur S et al. (2010) Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.

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18.

Limou S et al. (2014) APOL1 kidney risk alleles: population genetics and disease associations.

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19.

OMIM.ORG article

Omim 603743 [^]
20.

Orphanet article

Orphanet ID 240672 [^]
21.

NCBI article

NCBI 8542 [^]
22.

Wikipedia article

Wikipedia EN (Apolipoprotein_L1) [^]
Update: April 29, 2019