SUN-268 SURFACTANT PROTEIN-D (SP-D) GENE POLYMORPHISM INFLUENCES THE RISK OF ATHEROSCLEROSIS IN BLACK SOUTH AFRICAN CKD PATIENTS

Abstract

Atherosclerosis is increasingly being recognised as a polygenic disease where complex interactions between genetic and environmental factors play an important role. Because chronic low-grade inflammation is common to both chronic kidney disease (CKD) and cardiovascular disease (CVD), we hypothesized that inflammatory genetic markers would enhance the susceptibility for atherosclerosis in CKD patients. In this study, we evaluated a cohort of CKD patients for different genes of importance for inflammation that individually have shown a correlation to atherosclerosis. A total of 120 CKD patients and 40 healthy controls were enrolled. Five polymorphisms in three different genes were analysed: myeloperoxidase (MPO) – 129G/A and – 463G/A, surfactant protein D (SP-D) SP-D Met11Thr and SP-D Thr160Ala, and regulated upon normal T-cell expressed and secreted (CCL5) – 403G/A. Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasonography. The SP-D Thr160Ala (OR, 3.19) and CCL5– 403 (OR, 1.40) polymorphisms were significantly commoner among the CKD patients compared to the controls (Table 1). At CIMT evaluation, 71 patients (57.3%) had subclinical atherosclerosis. The SP-D Thr160Ala polymorphism was significantly associated with atherosclerosis (OR, 3.08; 95% CI: 1.07–8.87, p=0.037), and this relationship remained after adjustment for age, gender, smoking and cholesterol and mean arterial blood pressure. No associations were found for MPO – 129G/A, MPO– 463G/A, SP-D Met11Thr and CCL5 (Table 2). Table 1Genotype frequenciesPolymorphismsNumber of participantsCKD patientsControlsP valueMPO -129GGGACKD=120, controls=39118 (98.3%)2 (1.7%)39 (100%)0 (0%)0.568MPO - 463GGGA or AACKD=120, controls=3946 (38.3%)74 (61.7%)16 (41.0%)23 (69.0%0.765SP-D Met11ThrCCCT or TTCKD=120, controls=399 (7.5%)111 (92.5%)8 (20.5%)31 (79.5%)0.022SP-D 160 Thr160AlaGGAG or AACKD=120, controls=4099 (82.5%)21 (17.5%)38 (95%)2 (5%)0.038CCL5 - 403GGGA or AACKD=114, controls=3818 (15.8%)96 (84.2%)0 (0%)38 (100%)0.009 Open table in a new tab Table 2Association between candidate gene polymorphisms and atherosclerosisPolymorphismOdds ratio (95% confidence interval)P valueMPO – 129GG versus GA1.40 (0.09 – 21.86)0.810MPO -463GG versus GA/AA1.19 (0.90 – 1.57)0.228SP-D Met11ThrCC versus CT/TT0.96 (0.86 – 1.07)0.410SP-D 160 Thr160AlaGG versus AG/AA2.20 (1.00 – 4.91)0.048CCL5GG versus GA/AA1.02 (0.87 – 1.20)0.826 Open table in a new tab In this study, carriers of SP-D Thr160Ala genotype were more susceptible to atherosclerosis. The data support previous observations that SP-D plays a role in the aetiology of atherosclerotic disease development. Therefore, the SP-D 160 Thr160Ala genotype might perhaps be useful as biomarker in predicting atherosclerosis susceptibility.