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Saleheen, Danish; Soranzo, Nicole; Rasheed, Asif; Scharnagl, Hubert; Gwilliam, Rhian; Alexander, Myriam; Inouye, Michael; Zaidi, Moazzam; Potter, Simon; Haycock, Philip; Bumpstead, Suzanna; Kaptoge, Stephen; Di Angelantonio, Emanuele; Sarwar, Nadeem; Hunt, Sarah E.; Sheikh, Nasir; Shah, Nabi; Samuel, Maria; Haider, Shajjia Razi; Murtaza, Muhammed; Thompson, Alexander; Gobin, Reeta; Butterworth, Adam; Ahmad, Usman; [...]

Genetic Determinants of Major Blood Lipids in Pakistanis Compared With Europeans

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  • Medientyp: E-Artikel
  • Titel: Genetic Determinants of Major Blood Lipids in Pakistanis Compared With Europeans
  • Beteiligte: Saleheen, Danish; Soranzo, Nicole; Rasheed, Asif; Scharnagl, Hubert; Gwilliam, Rhian; Alexander, Myriam; Inouye, Michael; Zaidi, Moazzam; Potter, Simon; Haycock, Philip; Bumpstead, Suzanna; Kaptoge, Stephen; Di Angelantonio, Emanuele; Sarwar, Nadeem; Hunt, Sarah E.; Sheikh, Nasir; Shah, Nabi; Samuel, Maria; Haider, Shajjia Razi; Murtaza, Muhammed; Thompson, Alexander; Gobin, Reeta; Butterworth, Adam; Ahmad, Usman; [...]
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2010
  • Erschienen in: Circulation: Cardiovascular Genetics
  • Sprache: Englisch
  • DOI: 10.1161/circgenetics.109.906180
  • ISSN: 1942-325X; 1942-3268
  • Schlagwörter: Genetics (clinical) ; Cardiology and Cardiovascular Medicine ; Genetics
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec> <jats:title>Background—</jats:title> <jats:p>Evidence is sparse about the genetic determinants of major lipids in Pakistanis.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as <jats:italic>CETP</jats:italic> associated with HDL-C levels (rs711752; <jats:italic>P</jats:italic> &lt;10 <jats:sup>−13</jats:sup> ), <jats:italic>APOA5/ZNF259</jats:italic> (rs651821; <jats:italic>P</jats:italic> &lt;10 <jats:sup>−13</jats:sup> ) and <jats:italic>GCKR</jats:italic> (rs1260326; <jats:italic>P</jats:italic> &lt;10 <jats:sup>−13</jats:sup> ) with triglyceride levels; and <jats:italic>CELSR2</jats:italic> variants with LDL-C levels (rs646776; <jats:italic>P</jats:italic> &lt;10 <jats:sup>−9</jats:sup> ). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in <jats:italic>APOA5</jats:italic> among Pakistanis was higher and its impact on triglyceride concentration was greater ( <jats:italic>P</jats:italic> -value for difference &lt;10 <jats:sup>−4</jats:sup> ). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang