BACKGROUND: Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. METHODS: Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype. RESULTS: The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P = 0.044) and non-diabetic (OR: 1.369, P = 0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P = 0.019), but not in non-diabetics (P = 0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P = 0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80 ± 17.20 vs. 23.09 ± 21.63, P = 0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA(1c), or inflammatory cytokines for diabetic or non-diabetic patients with CAD. CONCLUSIONS: This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.
BACKGROUND: Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. METHODS: Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype. RESULTS: The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P = 0.044) and non-diabetic (OR: 1.369, P = 0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P = 0.019), but not in non-diabetics (P = 0.126). Among diabeticpatients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P = 0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80 ± 17.20 vs. 23.09 ± 21.63, P = 0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA(1c), or inflammatory cytokines for diabetic or non-diabeticpatients with CAD. CONCLUSIONS: This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabeticpatients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabeticpatients through a novel biological pathway unrelated to glucose metabolism or inflammation.
Authors: Muhammad S Munir; Zhen Wang; Fares Alahdab; Mark W Steffen; Patricia J Erwin; Iftikhar J Kullo; Mohammad Hassan Murad Journal: BMC Med Genet Date: 2014-06-06 Impact factor: 2.103
Authors: Kenneth Chan; Riyaz S Patel; Paul Newcombe; Christopher P Nelson; Atif Qasim; Stephen E Epstein; Susan Burnett; Viola L Vaccarino; A Maziar Zafari; Svati H Shah; Jeffrey L Anderson; John F Carlquist; Jaana Hartiala; Hooman Allayee; Kunihiko Hinohara; Bok-Soo Lee; Anna Erl; Katrina L Ellis; Anuj Goel; Arne S Schaefer; Nour Eddine El Mokhtari; Benjamin A Goldstein; Mark A Hlatky; Alan S Go; Gong-Qing Shen; Yan Gong; Carl Pepine; Ross C Laxton; John C Whittaker; W H Wilson Tang; Julie A Johnson; Qing K Wang; Themistocles L Assimes; Ute Nöthlings; Martin Farrall; Hugh Watkins; A Mark Richards; Vicky A Cameron; Axel Muendlein; Heinz Drexel; Werner Koch; Jeong Euy Park; Akinori Kimura; Wei-feng Shen; Iain A Simpson; Stanley L Hazen; Benjamin D Horne; Elizabeth R Hauser; Arshed A Quyyumi; Muredach P Reilly; Nilesh J Samani; Shu Ye Journal: J Am Coll Cardiol Date: 2013-01-23 Impact factor: 24.094
Authors: Anna Szpakowicz; Witold Pepinski; Ewa Waszkiewicz; Dominika Maciorkowska; Małgorzata Skawronska; Anna Niemcunowicz-Janica; Robert Milewski; Sławomir Dobrzycki; Włodzimierz Jerzy Musial; Karol Adam Kaminski Journal: PLoS One Date: 2013-09-12 Impact factor: 3.240
Authors: Anna Szpakowicz; Marek Kiliszek; Witold Pepinski; Ewa Waszkiewicz; Maria Franaszczyk; Małgorzata Skawronska; Rafal Ploski; Anna Niemcunowicz-Janica; Sławomir Dobrzycki; Grzegorz Opolski; Włodzimierz Jerzy Musial; Karol Adam Kaminski Journal: PLoS One Date: 2014-08-08 Impact factor: 3.240