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- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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- Zhang, DY, et al.
(författare)
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Genetic and functional effects of membrane metalloendopeptidase on diabetic nephropathy development
- 2011
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 34:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Vasopeptidase as an agent inhibits membrane metalloendopeptidase (MME, also known as neutral endopeptidase). MME is widely distributed in the body and particularly abundant in the kidney. The <i>MME </i>gene is located on chromosome 3q25.1 within a linkage region for diabetic nephropathy (DN). The present study aims to evaluate the genetic and functional effects of MME in the development of DN. <i>Methods:</i> A case-control genetic study of the<i> MME</i> gene in type 1 diabetes (T1D) patients with and without DN (n = 578/599) was performed. All subjects were selected from the Genetics of Kidneys in Diabetes study. Genotyping was performed with TagMan allelic discrimination. <i>Mme </i>mRNA and protein expression levels in kidney tissues of db/db mice at the ages of 5, 12 and 26 weeks were analyzed with TaqMan real-time RT-PCR and Western blot. <i>Results:</i> The haplotype A-C constructed with single nucleotide polymorphisms (SNPs) rs3796268A/G and rs3773885C/T in the <i>MME</i> gene was found to be associated with DN (p = 0.015, OR = 1.33, 95% CI 1.05–1.68) in female T1D patients. Further analyses of renal traits in T1D patients with DN and end-stage renal disease according to the genotypes of SNP rs3773885 indicated that the C allele carriers had higher serum creatinine levels compared to the subjects carrying T allele in both females and males. <i>Mme </i>expression at mRNA and protein levels was upregulated in kidneys of db/db mice at the ages of 12 and 26 weeks (p = 0.017 and <0.001) but not at the age of 5 weeks compared to the controls. <i>Conclusions:</i> The present study provides the first evidence that <i>MME </i>has genetic and biological effects on the development of DN, and suggests that the inhibition of <i>MME </i>expression in the kidney with the agent of vasopeptidase may be a useful therapeutic approach for this disease.
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