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, Hakeem Abdul, Zaman Khan Shah, Kundi Assadullah, Yaqoob Zia, Cheema Liaquat Ali, Qamar Nadeem, Faruqui Azhar, Mallick Nadeem Hayat, Azhar Muhammad, Samad Abdus, Ishaq Muhammad, Rasheed Syed Zahed, Jooma Rashid, Niazi Jawaid Hassan, Gardezi Ali Raza, Memon Nazir Ahmed, Ghaffar Abdul, Rehman Fazal-ur, Hoffmann Michael Marcus, Renner Wilfried, Kleber Marcus E, Grammer Tanja B, Stephens Jonathon, Attwood Anthony, Koch Kerstin, Hussain Mustafa, Kumar Kishore, Saleem Asim, Kumar Kishwar, Daood Muhammad Salman, Gul Aftab Alam, Abbas Shahid, Zafar Junaid, Shahid Faisal, Bhatti Shahzad Majeed, Ali Syed Saadat, Muhammad Fahim, Sagoo Gurdeep, Bray Sarah, McGinnis Ralph, Dudbridge Frank, Winkelmann Bernhard R, Böehm Bernhard, Thompson Simon, Ouwehand Willem, März Winfried, Frossard Philippe, Danesh John, Deloukas Panos
Center for Non-Communicable Diseases Karachi, Pakistan.
Circ Cardiovasc Genet. 2010 Aug;3(4):348-57. doi: 10.1161/CIRCGENETICS.109.906180. Epub 2010 Jun 22.
Evidence is sparse about the genetic determinants of major lipids in Pakistanis.
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)).
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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