BACKGROUND: Low serum uric acid (UA) levels have been associated with increased Parkinson's disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD. METHODS: We genotyped SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A+SCGN rs742132, and SLC16A9 rs12356193 in 1061 PD patients and 754 controls. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of PD-risk alleles (range, 2-15) associated to lower serum UA levels. Serum UA levels were measured in a subgroup of 365 PD cases and 132 controls. RESULTS: Serum UA levels were significantly lower in men with PD than in controls. Subjects (both men and women) carrying more than 9 risk alleles (third GRS tertile) had a 1.5 higher risk of developing PD than subjects with less than 8 risk alleles (first GRS tertile). An inverse correlation was observed between higher GRS and lower serum UA concentration in both men and women. CONCLUSIONS: Genetic variability influencing serum UA levels might modify susceptibility to PD.
BACKGROUND: Low serum uric acid (UA) levels have been associated with increased Parkinson's disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD. METHODS: We genotyped SLC2A9rs734553, ABCG2rs2231142, SLC17A1rs1183201, SLC22A11rs17300741, SLC22A12rs505802, GCKRrs780094, PDZK1rs12129861, LRRC16A+SCGNrs742132, and SLC16A9rs12356193 in 1061 PDpatients and 754 controls. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of PD-risk alleles (range, 2-15) associated to lower serum UA levels. Serum UA levels were measured in a subgroup of 365 PD cases and 132 controls. RESULTS: Serum UA levels were significantly lower in men with PD than in controls. Subjects (both men and women) carrying more than 9 risk alleles (third GRS tertile) had a 1.5 higher risk of developing PD than subjects with less than 8 risk alleles (first GRS tertile). An inverse correlation was observed between higher GRS and lower serum UA concentration in both men and women. CONCLUSIONS: Genetic variability influencing serum UA levels might modify susceptibility to PD.
Authors: Kelly Claire Simon; Shirley Eberly; Xiang Gao; David Oakes; Caroline M Tanner; Ira Shoulson; Stanley Fahn; Michael A Schwarzschild; Alberto Ascherio Journal: Ann Neurol Date: 2014-10-03 Impact factor: 10.422