| Differential effects of MYH9 and APOL1 risk variants on FRMD3 Association with Diabetic ESRD in African Americans. | |
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MedLine Citation:
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PMID: 21698141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9-a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E⁻⁷ additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E⁻⁴). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes. |
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Authors:
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Barry I Freedman; Carl D Langefeld; Lingyi Lu; Jasmin Divers; Mary E Comeau; Jeffrey B Kopp; Cheryl A Winkler; George W Nelson; Randall C Johnson; Nicholette D Palmer; Pamela J Hicks; Meredith A Bostrom; Jessica N Cooke; Caitrin W McDonough; Donald W Bowden |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2011-06-16 |
Journal Detail:
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Title: PLoS genetics Volume: 7 ISSN: 1553-7404 ISO Abbreviation: PLoS Genet. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-23 Completed Date: 2011-10-31 Revised Date: 2012-05-21 |
Medline Journal Info:
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Nlm Unique ID: 101239074 Medline TA: PLoS Genet Country: United States |
Other Details:
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Languages: eng Pagination: e1002150 Citation Subset: IM |
Affiliation:
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Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. bfreedma@wakehealth.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult African Americans / genetics* Aged Apolipoproteins / genetics* Chromosomes, Human, Pair 22 / genetics Diabetes Mellitus, Type 2 / complications, genetics Diabetic Nephropathies / etiology, genetics* Female Gene Expression Regulation Genome-Wide Association Study Haplotypes Humans Kidney Failure, Chronic / etiology, genetics* Lipoproteins, HDL / genetics* Male Middle Aged Molecular Motor Proteins / genetics* Myosin Heavy Chains / genetics* Polymorphism, Single Nucleotide / genetics Tumor Suppressor Proteins / genetics*, metabolism* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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M01 RR07122/RR/NCRR NIH HHS; R01 DK053591/DK/NIDDK NIH HHS; R01 DK066358/DK/NIDDK NIH HHS; R01 DK070941/DK/NIDDK NIH HHS; R01 DK070941/DK/NIDDK NIH HHS; R01 DK070941-06/DK/NIDDK NIH HHS; R01 DK084149/DK/NIDDK NIH HHS; R01 DK084149/DK/NIDDK NIH HHS; R01 HL56266/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/APOL1 protein, human; 0/Apolipoproteins; 0/FRMD3 protein, human; 0/Lipoproteins, HDL; 0/MYH9 protein, human; 0/Molecular Motor Proteins; 0/Myosin Heavy Chains; 0/Tumor Suppressor Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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