Objectives: While hemoglobin A1c (HbA1c) is a well-established risk factor of diabetic retinopathy (DR), it only accounts for limited variation in DR risk. Recent genome-wide association studies (GWAS) have identified some susceptibility single nucleotide polymorphisms (SNPs) for DR. This study aimed to evaluate the possible SNPxHbA1c interaction for the risk of sight-threatening DR (STDR) among patients with type 2 diabetes (T2DM).
Methods: Sixty-nine SNPs that showed top association signals (P<5x10-4; r2<0.9) in previous GWAS of DR were genotyped in 1106 STDR cases and 2069 non-DR controls. The associations between the SNPs and STDR were examined by multiple logistic regression analyses with adjustment for the traditional risk factors. HbA1c level was dichotomized according to a cut-off of 7% as suggested for an optimal glycemic control of diabetes. Interaction with HbA1c was examined by implementing an interaction term of SNP x dichotomized HbA1c in the logistic regression model.
Results: COL5A1 rs59126004 (P=0.016;OR=0.82), IGSF21-KLHDC7A rs3007729 (P=0.022;OR=0.86), LOC728275-LOC728316 rs227455 (P=0.031;OR=0.88), C6orf170 rs17083119 (P=0.035;OR=0.82) and SLC25A32 rs3098241 (P=0.046;OR=0.88) showed significant associations with STDR. Among these, COL5A1 rs59126004 also showed a significant interaction with HbA1c for the risk of STDR (Pinteraction=0.002). Stratified analysis showed that the minor allele of this SNP was associated with a reduced risk of STDR only in the patients with HbA1c <7% (P=1.79x10-4; OR=0.58), but not in patients with HbA1c ≥7%.
Conclusions: We have demonstrated a potential interaction between the COL5A1 rs59126004 and HbA1c for the susceptibility to STDR. Further studies to validate our findings are warranted.
K. Ng: None. C. Lee: None. Y. Woo: None. H. Fong: None. R. Wong: None. K.S. Lam: None. C.Y. Cheung: None.
Hong Kong Health and Medical Research Fund; Hong Kong Special Administrative Region