Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

نویسندگان

  • Danish Saleheen
  • Nicole Soranzo
  • Asif Rasheed
  • Hubert Scharnagl
  • Rhian Gwilliam
  • Myriam Alexander
  • Michael Inouye
  • Moazzam Zaidi
  • Simon Potter
  • Philip Haycock
  • Suzanna Bumpstead
  • Stephen Kaptoge
  • Emanuele Di Angelantonio
  • Nadeem Sarwar
  • Sarah E Hunt
  • Nasir Sheikh
  • Nabi Shah
  • Maria Samuel
  • Shajjia Razi Haider
  • Muhammed Murtaza
  • Alexander Thompson
  • Reeta Gobin
  • Adam Butterworth
  • Usman Ahmad
  • Abdul Hakeem
  • Khan Shah Zaman
  • Assadullah Kundi
  • Zia Yaqoob
  • Liaquat Ali Cheema
  • Nadeem Qamar
  • Azhar Faruqui
  • Nadeem Hayat Mallick
  • Muhammad Azhar
  • Abdus Samad
  • Muhammad Ishaq
  • Syed Zahed Rasheed
  • Rashid Jooma
  • Jawaid Hassan Niazi
  • Ali Raza Gardezi
  • Nazir Ahmed Memon
  • Abdul Ghaffar
  • Fazal-ur Rehman
  • Michael Marcus Hoffmann
  • Wilfried Renner
  • Marcus E Kleber
  • Tanja B Grammer
  • Jonathon Stephens
  • Anthony Attwood
  • Kerstin Koch
  • Mustafa Hussain
  • Kishore Kumar
  • Asim Saleem
  • Kishwar Kumar
  • Muhammad Salman Daood
  • Aftab Alam Gul
  • Shahid Abbas
  • Junaid Zafar
  • Faisal Shahid
  • Shahzad Majeed Bhatti
  • Syed Saadat Ali
  • Fahim Muhammad
  • Gurdeep Sagoo
  • Sarah Bray
  • Ralph McGinnis
  • Frank Dudbridge
  • Bernhard R Winkelmann
  • Bernhard Böehm
  • Simon Thompson
  • Willem Ouwehand
  • Winfried März
  • Philippe Frossard
  • John Danesh
  • Panos Deloukas
چکیده

BACKGROUND Evidence is sparse about the genetic determinants of major lipids in Pakistanis. METHODS AND RESULTS 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 CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). 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 APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). CONCLUSIONS 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.

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عنوان ژورنال:
  • Circulation. Cardiovascular genetics

دوره 3 4  شماره 

صفحات  -

تاریخ انتشار 2010