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APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy.
J Am Soc Nephrol 2011; 22(11):1991-6JA

Abstract

A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated MYH9, more recent analyses localized the strongest association within the neighboring APOL1 gene. In this replication study, we examined the six top-most associated variants in APOL1 and MYH9 in an independent cohort of African Americans with various nephropathies (44 with FSGS, 21 with HIVAN, 32 with IgA nephropathy, and 74 healthy controls). All six variants associated with FSGS and HIVAN (additive ORs, 1.8 to 3.0; P values 3 × 10(-2) to 5 × 10(-5)) but not with IgA nephropathy. In conditional and haplotype analyses, two APOL1 haplotypes accounted for virtually all of the association with FSGS and HIVAN on chromosome 22q13 (haplotype P value = 5.6 × 10(-8)). To assess the role of MYH9 deficiency in nephropathy, we crossbred Myh9-haploinsufficient mice (Myh9(+/-)) with HIV-1 transgenic mice. Myh9(+/-) mice were healthy and did not demonstrate overt proteinuria or nephropathy, irrespective of the presence of the HIV-1 transgene. These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans.

Authors+Show Affiliations

Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21997397

Citation

Papeta, Natalia, et al. "APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy." Journal of the American Society of Nephrology : JASN, vol. 22, no. 11, 2011, pp. 1991-6.
Papeta N, Kiryluk K, Patel A, et al. APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. J Am Soc Nephrol. 2011;22(11):1991-6.
Papeta, N., Kiryluk, K., Patel, A., Sterken, R., Kacak, N., Snyder, H. J., ... Gharavi, A. G. (2011). APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. Journal of the American Society of Nephrology : JASN, 22(11), pp. 1991-6. doi:10.1681/ASN.2011040434.
Papeta N, et al. APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy. J Am Soc Nephrol. 2011;22(11):1991-6. PubMed PMID: 21997397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. AU - Papeta,Natalia, AU - Kiryluk,Krzysztof, AU - Patel,Ami, AU - Sterken,Roel, AU - Kacak,Nilgun, AU - Snyder,Holly J, AU - Imus,Phil H, AU - Mhatre,Anand N, AU - Lawani,Anil K, AU - Julian,Bruce A, AU - Wyatt,Robert J, AU - Novak,Jan, AU - Wyatt,Christina M, AU - Ross,Michael J, AU - Winston,Jonathan A, AU - Klotman,Mary E, AU - Cohen,David J, AU - Appel,Gerald B, AU - D'Agati,Vivette D, AU - Klotman,Paul E, AU - Gharavi,Ali G, Y1 - 2011/10/13/ PY - 2011/10/15/entrez PY - 2011/10/15/pubmed PY - 2011/12/22/medline SP - 1991 EP - 6 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 22 IS - 11 N2 - A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated MYH9, more recent analyses localized the strongest association within the neighboring APOL1 gene. In this replication study, we examined the six top-most associated variants in APOL1 and MYH9 in an independent cohort of African Americans with various nephropathies (44 with FSGS, 21 with HIVAN, 32 with IgA nephropathy, and 74 healthy controls). All six variants associated with FSGS and HIVAN (additive ORs, 1.8 to 3.0; P values 3 × 10(-2) to 5 × 10(-5)) but not with IgA nephropathy. In conditional and haplotype analyses, two APOL1 haplotypes accounted for virtually all of the association with FSGS and HIVAN on chromosome 22q13 (haplotype P value = 5.6 × 10(-8)). To assess the role of MYH9 deficiency in nephropathy, we crossbred Myh9-haploinsufficient mice (Myh9(+/-)) with HIV-1 transgenic mice. Myh9(+/-) mice were healthy and did not demonstrate overt proteinuria or nephropathy, irrespective of the presence of the HIV-1 transgene. These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans. SN - 1533-3450 UR - https://www.unboundmedicine.com/medline/citation/21997397/APOL1_variants_increase_risk_for_FSGS_and_HIVAN_but_not_IgA_nephropathy_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=21997397 DB - PRIME DP - Unbound Medicine ER -