Genetic variability related to serum uric acid concentration and risk of Parkinson's disease
Funding agencies: Marqués de Valdecilla Foundation-IFIMAV (CFR 05/11 to I.G.-A.); Instituto de Investigación Carlos III (FI12/00229 to I.G.-A.); Fondo de Investigación Sanitaria (Instituto de Investigación Carlos III) (PI11/00228 to J.I.); Ministerio de Economía y Competitividad de España (SAF2007–60700 to S.J., F.C., P.G.-G., P.M.); Instituto de Salud Carlos III (PI10/01674 and CP08/00174 to S.J., F.C., P.G.-G., P.M.); Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526 and CTS-7685 to S.J., F.C., P.G.-G., P.M.); Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0377/2007, PI-0741/2010, and PI-0437–2012 to S.J., F.C., P.G.-G., P.M.); Sociedad Andaluza de Neurología (to S.J., F.C., P.G.-G., P.M.); Jacques and Gloria Gossweiler Foundation (to S.J., F.C., P.G.-G., P.M.); Fundación Alicia Koplowitz (to S.J., F.C., P.G.-G., P.M.); “Miguel Servet” program from the Instituto de Salud Carlos III (to P.G.-G.); Marqués de Valdecilla Foundation-IFIMAV (WLA 04/11 to M.S.).
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
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.
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.
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.
Genetic variability influencing serum UA levels might modify susceptibility to PD. © 2013 International Parkinson and Movement Disorder Society