The role of C-reactive protein genetic variability in the onset of carotid artery disease and renal function impairment in patients with diabetes mellitus type 2 Stavroula Papaoikonomou 1 , Dimitris Tousoulis ⁎ , 1 , Nikolaos Tentolouris, Dimitris Papadogiannis, Antigoni Miliou, George Hatzis, Nikolaos Papageorgiou, Charalambos Antoniades, Christodoulos Stefanadis 1st Cardiology Department, Athens University Medical School, Greece article info Article history: Received 8 April 2013 Accepted 4 May 2013 Available online 2 June 2013 Keywords: C-reactive protein Carotid artery disease Renal function Diabetes mellitus The role of diabetes mellitus (DM) in cardiovascular disease is well established and currently is considered as an equivalent of coronary artery disease. Studies have also reported that DM is associated with the prevalence of occlusive carotid artery disease (AD) [1] as well as the grade carotid artery stenosis [2]. In addition, DM is related to impaired renal function via several mechanisms [3]. During the last years novel data have arisen for the role of genetics in the initiation and progression of carotid AD [4–8] as well as for impaired renal function [9,10]. However, scarce data exist regarding genetic poly- morphisms in patients with diabetes mellitus and their role in carotid artery disease and renal function. Thus, in the present study we examined the potential role of a single nucleotide polymorphism (SNP) on C-reactive protein (CRP) gene in the onset of carotid AD and impaired renal function in patients with diabetes mellitus type 2. Our study population consisted of 430 patients with DM2 (docu- mented for carotid AD or not). Subjects were characterized as patients with DM2 if fasting plasma glucose levels were ≥126 mg/dl, or 2-hour post glucose loading plasma levels were ≥200 mg/d according to the American Diabetes Association [11]. Carotid artery disease was evaluated based on history of transient ischemic attack or stroke, important degree of carotid stenosis in Doppler ultrasonography or blowing existence or interventional procedure of carotid revasculariza- tion. Subjects were considered to have systemic hypertension if their systolic and/or diastolic blood pressure was ≥140 and/or ≥90 mm Hg on two different occasions. Moreover subjects were considered to have systemic hypertension if they were currently being treated with anti-hypertensive drugs or when a significant history of hypertension was present [12]. Subjects were considered to have dyslipidemia if total cholesterol levels ≥200 mg/dl were revealed in biochemical tests or if they were already treated with antihyperlipidemic agents [13]. Current smokers were regarded as subjects smoking 1–10 cigarettes/day for at least the last year [14]. In the exclusion criteria we included any acute or chronic inflammatory disease, malignancies, and renal or liver failure. Glomerular filtration rate (GFR) was measured by the appropriate formula. The study was approved by the institutional ethics committees, and an informed consent was given by all the participants. Venous blood samples were centrifuged at 3500 rpm at 4 °C for 15 min, and plasma or serum was collected and stored at -80 °C until assayed. Serum concentrations of lipids were determined by using colorimetric enzymatic method in a Technicon automatic analyzer RA- ⁎ Corresponding author at: Athens University Medical School, Hippokration Hospital, Vasilisis Sofias 114, 115 28 Athens, Greece. Tel.: +30 2132088099; fax: +30 2132088676. E-mail address: drtousoulis@hotmail.com (D. Tousoulis). Table 1 Clinical and demographic characteristics of subjects with type 2 diabetes mellitus and or no carotid artery disease by CRP3872AG polymorphism. Carotid AD No carotid AD CRP3872AG n (%) 58(13.5) 372(86.5) Gender (men/women) n (%) 36(62.1)/22(37.9) 182(48.9)/190(51.1) p = 0.067 Hypertension (yes/no) n (%) 49(84.5)/9(15.5) 279(75.0)/93(25.0) p = 0.136 Smokers (yes/no) n (%) 11(19.0)/47(81.0) 60(16.1)/312(83.9) p = 0.566 History of smoking (yes/no) n% 28(48.3)/30(51.7) 113(30.4)/259(69.6) p = 0.010 Age (years) 69 ± 7.217 66.15 ± 10.268 p = 0.033 Body mass index (kg/m 2 ) 27.74 ± 5.349 29.19 ± 4.931 p = 0.041 Waist (cm) 98.43 ± 12.339 100.07 ± 12.655 p = 0.338 HbA1c (%) 7.34 ± 1.273 7.37 ± 1.511 p = 0.885 Glucose (mg/dl) 155.33 ± 72.299 149.79 ± 68.198 p = 0.571 Tchol (mg/dl) 182.17 ± 49.254 188.81 ± 40.914 p = 0.268 LDL cholesterol (mg/dl) 100.24 ± 38.043 111.12 ± 36.925 p = 0.038 HDL cholesterol (mg/dl) 47.45 ± 13.492 48.78 ± 13.437 p = 0.492 Triglycerides (mg/dl) a 129(96.5–160.0) 129(95.0–177.0) p = NS hs-CRP (mg/l) a 3.16(3.02–5.06) 3.16(3.02–3.84) p = NS log hs-CRP 0.61 ± 0.24 0.58 ± 0.22 p = 0.341 GFR (ml/min) 69.29 ± 26.317 84.26 ± 31.935 p = 0.001 SBP (mm Hg) 140.23 ± 18.786 134.46 ± 15.579 p = 0.011 DBP (mm Hg) 77.23 ± 11.819 76.70 ± 10.013 p = 0.715 All values are expressed as mean ± SD. Carotid AD: carotid artery disease. a Values were expressed as median (25–75th percentile). 4331 Letters to the Editor