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Articles by T. B Grammer
Total Records ( 2 ) for T. B Grammer
  D Saleheen , N Soranzo , A Rasheed , H Scharnagl , R Gwilliam , M Alexander , M Inouye , M Zaidi , S Potter , P Haycock , S Bumpstead , S Kaptoge , E Di Angelantonio , N Sarwar , S. E Hunt , N Sheikh , N Shah , M Samuel , S. R Haider , M Murtaza , A Thompson , R Gobin , A Butterworth , U Ahmad , A Hakeem , K. S Zaman , A Kundi , Z Yaqoob , L. A Cheema , N Qamar , A Faruqui , N. H Mallick , M Azhar , A Samad , M Ishaq , S. Z Rasheed , R Jooma , J. H Niazi , A. R Gardezi , N. A Memon , A Ghaffar , F. u Rehman , M. M Hoffmann , W Renner , M. E Kleber , T. B Grammer , J Stephens , A Attwood , K Koch , M Hussain , K Kumar , A Saleem , M. S Daood , A. A Gul , S Abbas , J Zafar , F Shahid , S. M Bhatti , S. S Ali , F Muhammad , G Sagoo , S Bray , R McGinnis , F Dudbridge , B. R Winkelmann , B Boehm , S Thompson , W Ouwehand , W Marz , P Frossard , J Danesh and P. Deloukas
  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.

  T. B Grammer , D Fuchs , B. O Boehm , B. R Winkelmann and W. Maerz
 

Background: Neopterin is produced upon activation of the cell-mediated immune response, and may be a novel risk marker for adverse outcomes resulting from coronary artery disease.

Methods: We measured neopterin in 1801 study participants with and 511 without angiographic coronary artery disease. Rates of death were determined after a median follow-up of 8.0 years.

Results: Estimated glomerular filtration rate and N-terminal pro-B–type natriuretic peptide (NT-proBNP) were the strongest predictors of neopterin. Neopterin was positively related to age and inversely related to LDL cholesterol, HDL cholesterol, and triglycerides. Use of lipid-lowering drugs lowered neopterin. Sex, body mass index, diabetes mellitus, hypertension, smoking status, Friesinger coronary score, and clinical instability at presentation were not associated with neopterin. Unlike C-reactive protein, neopterin was not increased in unstable angina pectoris, non–ST–elevation myocardial infarction, or ST-elevation myocardial infarction. In the third and fourth quartiles of neopterin, unadjusted hazard ratios for death from any cause were 1.94 (95% CI 1.44–2.61) and 3.32 (95% CI 2.53–4.30) compared to individuals in the first quartile, whereas hazard ratios for death from cardiovascular causes were 2.14 (95% CI 1.44–3.18) and 3.84 (95% CI 2.67–5.52), respectively. Neopterin remained predictive of total and cardiovascular mortality after adjusting for sex, age, body mass index, type 2 diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol, triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical status at presentation, but NT-proBNP substantially weakened this association.

Conclusions: Neopterin is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease.

 
 
 
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