A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
العنوان: | A genome-wide association meta-analysis on apolipoprotein A-IV concentrations |
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المؤلفون: | Lamina, C., Friedel, S., Coassin, S., Rueedi, R., Yousri, N.A., Seppälä, I., Gieger, C., Schönherr, S., Forer, L., Erhart, G., Kollerits, B., Marques-Vidal, P., Ried, J., Waeber, G., Bergmann, S., Dähnhardt, D., Stöckl, A., Kiechl, S., Raitakari, O.T., Kähönen, M., Willeit, J., Kedenko, L., Paulweber, B., Peters, A., Meitinger, T., Strauch, K., Study Group, K., Lehtimäki, T., Hunt, S.C., Vollenweider, P., Kronenberg, F. |
المصدر: | Human Molecular Genetics Hum. Mol. Genet. 25, 3635-3646 (2016) Human molecular genetics, vol. 25, no. 16, pp. 3635-3646 |
بيانات النشر: | Oxford University Press, 2016. |
سنة النشر: | 2016 |
مصطلحات موضوعية: | Male, Association Studies Articles, Cholesterol, HDL, nutritional and metabolic diseases, Kidney, Lipids, Polymorphism, Single Nucleotide, Humans, lipids (amino acids, peptides, and proteins), Female, Alleles, Apolipoproteins A, Triglycerides, Genome-Wide Association Study |
الوصف: | Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (-) (44)), rs5104 in APOA4 (P = 1.79 × 10(-)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(-)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (-) (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(-)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1460-2083 0964-6906 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::2e648e42cf9fe7c19d211b230a3b4623Test http://europepmc.org/articles/PMC5179953Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.pmid.dedup....2e648e42cf9fe7c19d211b230a3b4623 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14602083 09646906 |
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