Association study of AGER gene polymorphism and hypertension in Han Chinese population

Advanced glycation end products (AGEs) are produced by non-enzymatic glycation or glycoxidation of proteins, lipids and nucleic acids. The bond of AGEs and the receptor of AGE (AGER) in a pro-oxidant environment could induce immune and inflammation reaction involved in progress of microvascular disease. Accumulated evidence warrant further study on AGE-AGER pathway and genetic susceptibility to hypertension (HT).

We designed a two-stage association study to evaluate the association of AGER polymorphism and HT. In stage 1, seven tagSNPs were tested in 524 cases and 531 controls and the significant SNPs (P<0.05) would enter into stage 2 including 807 cases and 869 controls. Furthermore, joint analysis was performed for all 2731 subjects including 1331 cases and 1400 controls, and meta-analysis was applied to evaluate combined estimations from the subgroups of stage 1 and stage 2.

In stage 1, rs204994 had significant association with HT (P<0.05) and enter stage 2. Neither joint analysis nor meta-analysis found statistical association of rs204994 with HT after adjusted for the covariates in the whole population. However, further stratification analysis found that rs204994 was significantly associated with HT in <50years and ≥50years groups, ORs (95%CI) of dominant model were 1.623 (1.054-2.500) and 0.721 (0.546-0.952) respectively. No significant correlation was found between blood pressure and the polymorphisms of rs204994.

Our data suggests that age might modulate the genetic effects of variation of rs204994 in AGER on HT and further replications in other populations and functional studies should be warranted.