Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians: the Strong Heart Family Study.

MedStar author(s):
Citation: Journal of Hypertension. 32(5):1042-8; discussion 1049, 2014 May.PMID: 24569419Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Indians, North American | *Kidney Function Tests | *Receptors, Nicotinic/ge [Genetics] | Adult | Female | Glomerular Filtration Rate | Humans | Male | Middle Aged | Polymorphism, Single Nucleotide | Prospective Studies | Risk FactorsYear: 2014Local holdings: Available online from MWHC library: 1997 - presentISSN:
  • 0263-6352
Name of journal: Journal of hypertensionAbstract: BACKGROUND: Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial.CONCLUSION: Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians. The effects of these genetic variants on kidney function or damage are independent of traditional risk factors including cigarette smoking per se.METHODS: Using a gene-family approach, we investigated the joint association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney function in 3620 American Indians participating in the Strong Heart Family Study, independent of known risk factors. Kidney function was evaluated by estimated glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and chronic kidney disease. The joint impact of smoking-related variants was assessed using the weighted truncated product method.RESULTS: Multiple SNPs showed marginal individual effect on renal function variability, and only a few survive multiple comparison correction. In contrast, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant associations of the nAChR gene family with kidney function variables including estimated glomerular filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps < 0.0001) after adjusting for established risk factors including cigarette smoking.All authors: Cole SA, Franceschini N, Haack K, Howard BV, Lee ET, Li S, Umans JG, Yang J, Zhao J, Zhu YFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2015-03-17
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 24569419 Available 24569419

Available online from MWHC library: 1997 - present

BACKGROUND: Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial.

CONCLUSION: Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians. The effects of these genetic variants on kidney function or damage are independent of traditional risk factors including cigarette smoking per se.

METHODS: Using a gene-family approach, we investigated the joint association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney function in 3620 American Indians participating in the Strong Heart Family Study, independent of known risk factors. Kidney function was evaluated by estimated glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and chronic kidney disease. The joint impact of smoking-related variants was assessed using the weighted truncated product method.

RESULTS: Multiple SNPs showed marginal individual effect on renal function variability, and only a few survive multiple comparison correction. In contrast, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant associations of the nAChR gene family with kidney function variables including estimated glomerular filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps < 0.0001) after adjusting for established risk factors including cigarette smoking.

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