In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-07-19)
Abstract:
Chronic renal disease (CRD) associated with cardiovascular disease (CVD) and/or type 2 diabetes (T2D) is a significant problem in Aboriginal Australians. Whole exome sequencing data (N = 72) showed enrichment for ClinVar pathogenic variants in gene sets/pathways linking lipoprotein, lipid and glucose metabolism. The top Ingenuity Pathway Analysis canonical pathways were Farsenoid X Receptor and Retinoid Receptor (FXR/RXR; (P = 1.86 × 10 −7 ), Liver X Receptor and Retinoid Receptor (LXR/RXR; P = 2.88 × 10 −6 ), and atherosclerosis signalling (P = 3.80 × 10 −6 ). Top pathways/processes identified using Enrichr included: Reactome 2016 chylomicron-mediated lipid transport (P = 3.55 × 10 −7 ); Wiki 2016 statin (P = 8.29 × 10 −8 ); GO Biological Processes 2017 chylomicron remodelling (P = 1.92 × 10 −8 ). ClinVar arylsulfatase A pseudodeficiency (ARSA-PD) pathogenic variants were common, including the missense variant c.511 G 〉 A (p.Asp171Asn; rs74315466; frequency 0.44) only reported in Polynesians. This variant is in cis with known ARSA-PD 3′ regulatory c.*96 A 〉 G (rs6151429; frequency 0.47) and missense c.1055 A 〉 G (p.Asn352Ser; rs2071421; frequency 0.47) variants. These latter two variants are associated with T2D (risk haplotype GG; odds ratio 2.67; 95% CI 2.32–3.08; P = 2.43 × 10 −4 ) in genome-wide association data (N = 402), but are more strongly associated with quantitative traits (DBP, SBP, ACR, eGFR) for hypertension and renal function in non-diabetic than diabetic subgroups. Traits associated with CVD, CRD and T2D in Aboriginal Australians provide novel insight into function of ARSA-PD variants.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-29279-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2615211-3
