Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI, Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele-specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20-I25) and incidence of cerebrovascular diseases (I60-I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low-density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology.