Abstract 3930: Effects of Lymphotoxin-α Gene and Galectin 2 Gene Polymorphisms on Inflammatory Biomarkers and Risk of Coronary Heart Disease in US Men and Women
Background: The proinflammatory cytokine lymphotoxin-α (LTA) has multiple functions in regulation of the immune system and may contribute to the atherosclerotic process.
The aim of this study was to investigate whether the common A252G and A26C polymorphisms of the LTA gene and the C3279CT polymorphism of the galectin 2 (LGALS2) gene, which affects LTA secretion, are associated with inflammatory parameters (i.e. C-reactive protein, interleukin-6, soluble tumor necrosis factor receptor 1 and 2) and whether these polymorphisms are related to coronary heart disease (CHD) in US women and men.
Methods: We conducted a prospective nested case-control study within the Nurses’ Health Study and Health Professionals Follow-Up Study. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow-up respectively, and we matched controls 2:1 based on age and smoking.
Results: Except for the LGALS2 gene polymorphism, the distribution of alleles was similar in cases and controls. The LGALS2 gene variant modeled as a dominant genotype was significantly associated with a decreased risk for CHD in women (Odds ratio [95% confidence intervals]: 0.70 [0.50 – 0.97], p=0.03); this association remained after adjustment for diabetes, history of hypertension, body mass index, family history of myocardial infarction, HDL-cholesterol, LDL-cholesterol, CRP, IL-6, sTNF-R1, sTNF-R2 (0.58 [0.39 – 0.86], p=0.006). In addition, the LGALS2 polymorphism was directly associated with C-reactive protein levels in cases from both studies (p<0.05). The LTA gene polymorphisms were directly associated with levels of soluble tumor necrosis factor receptors in both women and men with CHD (p<0.05). However, no overall effect was demonstrated between LTA gene polymorphisms and risk for CHD.
Conclusion: The present study demonstrated an association between LTA and LGALS2 gene polymorphisms and markers of inflammation. In addition, the LGALS2 gene polymorphism was associated with a reduced risk for CHD in women. However, we did not find an overall association between LTA gene polymorphisms and risk of CHD in women and men.