title: Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.
abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.
authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Lin
authors.forename: I
authors.initials: I
authors.lastname: Adrianto
authors.forename: C J
authors.initials: CJ
authors.lastname: Lessard
authors.forename: J A
authors.initials: JA
authors.lastname: Kelly
authors.forename: K M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: J M
authors.initials: JM
authors.lastname: Guthridge
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
authors.forename: J-M
authors.initials: JM
authors.lastname: Anaya
authors.forename: M E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: B A
authors.initials: BA
authors.lastname: Pons-Estel
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Glenn
authors.forename: A
authors.initials: A
authors.lastname: Adler
authors.forename: S-C
authors.initials: SC
authors.lastname: Bae
authors.forename: S-Y
authors.initials: SY
authors.lastname: Park
authors.forename: S-Y
authors.initials: SY
authors.lastname: Bang
authors.forename: Y-W
authors.initials: YW
authors.lastname: Song
authors.forename: S A
authors.initials: SA
authors.lastname: Boackle
authors.forename: E E
authors.initials: EE
authors.lastname: Brown
authors.forename: J C
authors.initials: JC
authors.lastname: Edberg
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: M A
authors.initials: MA
authors.lastname: Petri
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
authors.forename: R
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
authors.forename: L M
authors.initials: LM
authors.lastname: Vila
authors.forename: G S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: D L
authors.initials: DL
authors.lastname: Kamen
authors.forename: J
authors.initials: J
authors.lastname: Ziegler
authors.forename: C O
authors.initials: CO
authors.lastname: Jacob
authors.forename: A
authors.initials: A
authors.lastname: Rasmussen
authors.forename: J A
authors.initials: JA
authors.lastname: James
authors.forename: R P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: J T
authors.initials: JT
authors.lastname: Merrill
authors.forename: T B
authors.initials: TB
authors.lastname: Niewold
authors.forename: R H
authors.initials: RH
authors.lastname: Scofield
authors.forename: A M
authors.initials: AM
authors.lastname: Stevens
authors.forename: B P
authors.initials: BP
authors.lastname: Tsao
authors.forename: T J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: K L
authors.initials: KL
authors.lastname: Moser
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
authors.forename: P M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: C G
authors.initials: CG
authors.lastname: Montgomery
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000235:genetics*; D008181:Lupus Nephritis / Q000208:ethnology* / Q000235:genetics*; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains