Six common genetic variants (rs2229094, rs1041981, rs1800630, rs1800629, rs361525, and rs1800610) in the TNF-LTA locus encoding the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha have been shown to be associated with various metabolic traits including susceptibility to type 2 diabetes, metabolic syndrome, insulin resistance, and increased body mass index (BMI) in Caucasians from different geographic locations and have yielded mixed results.
Possession of the IL-6 rs1800797 GG genotype by the LTA and TNF-alpha risk genotype carriers further increased risk of the MetS [OR 2.10 (CI 1.19-3.71) P = 0.009], fasting hyperglycemia [OR 2.65 (CI 1.12-6.28), P = 0.027], high systolic blood pressure [OR 1.99 (CI 1.07-3.72), P = 0.03], and abdominal obesity [OR 1.52 (CI 1.01-2.28), P = 0.04].
Homozygosity for rare alleles of the LTA 252A>G polymorphisms was associated with features of metabolic syndrome such as hyperinsulinemia, dyslipidemia, small LDL particle and low adiponectin level in CAD patients, suggesting that CAD patients with LTA 252GG are at high risk and needed an intensive intervention against further progression.
In this study, we used the galectin 2 (LGALS2) genotype, which affects LTA secretion but is located on another chromosome than the HLA gene cluster or TNF, to examine the relationship between the LTA pathway and traits of the metabolic syndrome.