title: An investigation of APOL1 risk genotypes and preterm birth in African American population cohorts.
abstract: BACKGROUND
  Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes. These risk variants are common in individuals of African ancestry but absent in other racial groups. Yet, the majority of individuals with two APOL1 risk alleles [high-risk (HR) genotype] do not have renal disease. It is critical to identify environmental and secondary genetic influences that, when combined with these alleles, lead to kidney disease. In a recent study of black children with glomerular disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) and Chronic Kidney Disease in Children Study (n = 104), we found that subjects with an HR genotype had a 4.6-fold increase in the odds of preterm birth as compared to those with a low risk (LR) genotype [odds ratio 4.6 (CI 1.4-15.5)]. There are known racial disparities in preterm birth, which itself is a known risk factor for chronic kidney disease and focal segmental glomerulosclerosis. Thus, we questioned whether an HR APOL1 genotype is associated with prematurity in the general African American population.
  
  
  METHODS
  We analyzed two publically available genetic datasets of preterm birth in African Americans, including 867 infants and 519 mothers from the Gene Environment Association Studies (GENEVA) study of preterm delivery and 960 mothers from the Boston Medical Center genome-wide association study of preterm birth. We performed multivariable analyses testing for association between HR APOL1 and birth outcomes.
  
  
  RESULTS
  In both studies, there was no association between HR APOL1 in mothers and prematurity, gestational age or birthweight. Additionally, in the GENEVA study, we saw no association between infant HR APOL1 and prematurity, gestational age or birthweight.
  
  
  CONCLUSIONS
  From these data, we conclude that the previously observed association between HR APOL1 and prematurity is specific to those with glomerular disease, suggesting prematurity may act as an additional risk factor in APOL1-associated renal disease.
authors.affiliation: Pediatric Nephrology, University ofMichigan School of Medicine, 3560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Robertson
authors.affiliation: Pediatric Nephrology, University ofMichigan School of Medicine, 3560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Gillies
authors.affiliation: Pediatric Nephrology, University ofMichigan School of Medicine, 3560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Rosemary K B
authors.initials: RKB
authors.lastname: Putler
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Ng
authors.affiliation: Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Reidy
authors.affiliation: Pediatric Nephrology, University ofMichigan School of Medicine, 3560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Crawford
authors.affiliation: Pediatric Nephrology, University ofMichigan School of Medicine, 3560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Sampson
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000075944:Apolipoprotein L1 / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications* / Q000235:genetics; D006801:Humans; D010641:Phenotype; D047928:Premature Birth / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1
keywords: CKD; epidemiology; ethnicity; pediatrics; prematurity; risk allele