Mutations in glucocerebrosidase (GBA) are a common risk factor for Parkinson's disease (PD). The scavenger receptor class B member 2 (SCARB2) gene encodes a receptor responsible for the transport of glucocerebrosidase (GCase) to the lysosome. Two common SNPs in linkage disequilibrium with SCARB2, rs6812193 and rs6825004, have been associated with PD and Lewy Body Disease in genome wide association studies. Whether these SNPs are associated with altered glucocerebrosidase enzymatic activity is unknown. Our objective was to determine whether SCARB2 SNPs are associated with PD and with reduced GCase activity. The GBA gene was fully sequenced, and the LRRK2 G2019S and SCARB2 rs6812193 and rs6825004 SNPs were genotyped in 548 PD patients and 272 controls. GCase activity in dried blood spots was measured by tandem mass spectrometry. We tested the association between SCARB2 genotypes and PD risk in regression models adjusted for gender, age, and LRRK2 G2019S and GBA mutation status. We compared GCase activity between participants with different genotypes at rs6812193 and rs6825004. Genotype at rs6812193 was associated with PD status. PD cases were less likely to carry the T allele than the C allele (OR=0.71; p=0.004), but GCase enzymatic activity was similar across rs6812193 genotypes (C/C: 11.88 μmol/l/h; C/T: 11.80 μmol/l/h; T/T: 12.02 μmol/l/h; p=0.867). Genotype at rs6825004 was not associated with either PD status or GCase activity. In conclusion, our results support an association between SCARB2 genotype at rs6812193 and PD, but suggest that the increased risk is not mediated by GCase activity.

中文翻译：

---

帕金森氏病中的SCARB2变体和葡萄糖脑苷脂酶活性。

葡萄糖脑苷脂酶（GBA）突变是帕金森氏病（PD）的常见危险因素。清除剂受体B类成员2（SCARB2）基因编码负责将葡萄糖脑苷脂酶（GCase）转运至溶酶体的受体。在全基因组关联研究中，与SCARB2连锁不平衡的两种常见SNP rs6812193和rs6825004与PD和路易体病相关。这些SNP是否与改变的葡萄糖脑苷脂酶的酶活性有关。我们的目标是确定SCARB2 SNP是否与PD相关，并与GCase活性降低有关。GBA基因已完全测序，并在548名PD患者和272名对照中对LRRK2 G2019S和SCARB2 rs6812193和rs6825004 SNP进行了基因分型。通过串联质谱法测量干血斑中的GCase活性。我们在针对性别，年龄以及LRRK2 G2019S和GBA突变状态调整的回归模型中测试了SCARB2基因型与PD风险之间的关联。我们在rs6812193和rs6825004处比较了具有不同基因型的参与者之间的GCase活性。rs6812193的基因型与PD状态相关。与C等位基因相比，PD病例携带T等位基因的可能性较小（OR = 0.71; p = 0.004），但是rs6812193基因型的GCase酶促活性相似（C / C：11.88μmol/ l / h; C / T：11.80 μmol/ l / h； T / T：12.02μmol/ l / h； p = 0.867）。rs6825004的基因型与PD状态或GCase活性均无关。总之，我们的结果支持rs6812193的SCARB2基因型与PD之间的关联，但表明增加的风险不是由GCase活性介导的。