Association of gene polymorphisms with myocardial infarction in individuals with or without conventional coronary risk factors.

The purpose of the present study was to assess the genetic risk for myocardial infarction (MI) in individuals with or without conventional coronary risk factors and thereby to contribute to the personalized prevention of MI in such individuals. The study population comprised 3483 unrelated Japanese individuals (1913 men, 1570 women). The 1192 subjects with MI (926 men, 266 women) and 2291 controls (987 men, 1304 women) either had or did not have conventional coronary risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 164 polymorphisms of 137 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that nine different polymorphisms were significantly (P<0.005) associated with MI among individuals with or without hypertension, hypercholesterolemia, or diabetes mellitus: 1018Cright curved arrow T of GP1BA, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, and Gright curved arrow A of UTS2 in hypertensive individuals; 2445Gright curved arrow A of FABP2, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, -11,377Cright curved arrow G of ACDC, Aright curved arrow G of AKAP10, 11,496Gright curved arrow A of F7, and 46Cright curved arrow T of F12 in individuals without hypercholesterolemia; 2445Gright curved arrow A of FABP2 in diabetic individuals; and -108/3Gright curved arrow 4G of IPF1 in nondiabetic individuals. Polymorphisms associated with MI may thus differ among individuals with different conventional coronary risk factors. Stratification of subjects on the basis of such risk factors may thus be important in order to achieve personalized prevention of MI with the use of genetic information.

Acute septic shock during pegylated-interferon and ribavirin therapy in a patient with chronic hepatitis C who underwent aortic graft replacement.

We report an autopsied case of a 59-year-old woman with acute septic shock from methicillin-resistant Staphylococcus aureus (MRSA) infection during combination therapy with pegylated-interferon-α-2b (PEG-IFNα-2b) and ribavirin. She underwent aortic graft replacement for the treatment of a dissecting aneurysm. We observed her latent infection closely for over a year following the operation. The clinical and laboratory examinations did not show any sign of infection. She then underwent PEG-IFNα-2b/ribavirin combination therapy. In her 17th week of therapy, she suddenly complained of high fever followed by a markedly rapid progression of sepsis and disseminated intravascular coagulation. She died of acute septic shock from MRSA infection on her fourth hospital day. Autopsy revealed abscess formation in the mediastinum around the artificial vessel graft. There was no obvious verruca on the internal surface of the replaced graft. Microscopic examination revealed numerous cocci along the thread in the suture of the graft. This clinical experience shows that combination therapy with PEG-IFNα-2b/ribavirin for the treatment of chronic hepatitis C should be given careful consideration when administered to patients who have undergone major vessel surgery, such as aortic graft replacement. Once the treatment has been started, infection should be monitored with particular care and frequent medical examinations.