Leucine rich repeat kinase 2 (LRRK2) gly2019ser mutation is absent in a second cohort of nigerian africans with parkinson disease

Abstract

To date the LRRK2 p.G2019S mutation remains the most common genetic cause of Parkinson disease (PD) worldwide. It accounts for up to 6% of familial and approximately 1.5% of sporadic cases. LRRK2 has a kinase enzymatic domain which provides an attractive potential target for drug therapies and LRRK2 kinase inhibitors are in development. Prevalence of the p.G2019S has a variable ethnic and geographic distribution, the highest was reported among Ashkenazi Jews (30% in patients with familial PD, 14% in sporadic PD, 2.0% in controls) and North African Berbers (37% in patients with familial PD, 41% in sporadic PD, and 1% in controls). Little is known about the frequency of the LRRK2 p.G2019S among populations in Sub Saharan Africa. Our group and others previously reported that the p.G2019S is absent in a small cohort from Nigerian PD patients and controls. Here we used Kompetitive Allele Specific PCR (KASP) assay to screen for the p.G2019S in a larger cohort of Black African PD patients (n =126) and healthy controls (n = 55) from Nigeria. Our analysis confirmed that all patients and controls are negative for the p.G2019S mutation. This report provides further evidence that the LRRK2 p.G2019S is not implicated in PD in black populations from Nigeria and support the notion that p.G2019S mutation originated after the early human dispersal from sub-Saharan Africa. Further studies using larger cohorts and advance sequencing technology are required to underpin the genetic causes of PD in this region.

Negative screening for 12 rare LRRK2 pathogenic variants in a cohort of Nigerians with Parkinson's disease

“…In this study we expanded on our previous enquiry regarding the role of rare LRRK2 variants in PD in persons of sub-Saharan African black ancestry by exploring a third cohort from Nigeria. We used an efficient, economical and accurate methodthe Kompetitive 22) We were unable to identify any pathogenic variants in both cohorts. In total, our group has screened 275 Nigerians with PD and 316 controls, and no pathogenic variants of LRRK2 have as yet been demonstrated.…”

“…A few studies including two from our group in Nigeria, one in Zambia, one in Ghana and several in South Africa have investigated the LRRK2 PD pathogenic variants in Sub-Saharan Africa. (21)(22)(23)(24)(25)(26)(27)(28)(29)(30) In the present report, we expand on our previous enquiry which focused only on LRRK2 p.gly2019ser in Nigeria, to explore the frequency of 12 pathogenic rare PD-associated LRRK2 variants including the p.gly2019ser in a new cohort of 92 Nigerians with PD and 210 ethnically matched controls.…”

“…Genotyping was performed using Kompetitive Allele-Specific Polymerase chain reaction (PCR) assay (KASP™, LGC Genomics. Herts, UK) as described previously (22,32). 12 single nucleotide polymorphisms (SNPs) were selected for genotyping namely: rs34637584(p.Gly2019Ser), rs34995376 (p.Arg1441His), rs74163686 (p.Asn1437His), rs35870237 (p.Ile2020Thr), rs35801418 (p.Tyr1699Cys), rs34410987 (p.Pro755Leu), rs34778348 (p.Gly2385Arg), rs281865052 (p.Met1869Val), rs34594498 (p.Ala419Val), rs33949390 (p.Arg1628Pro), rs35808389 (p.Leu1114Leu), rs34805604 (p.Ile1122Val).…”

Ethnic Variation in the Manifestation of Parkinson’s Disease: A Narrative Review

“…For example, LRRK2 p.G2019S is the most common genetic cause of PD worldwide and accounts for 1% of sporadic PD and 4% of familial PD [126]. However the prevalence of LRRK2 p.G2019S is 30-39% in North African Berbers with PD and 26% in Ashkenazi Jewish PD cases, yet it seems to be completely absent in Nigerian PD patients [127][128][129].…”

Prevalence of ten LRRK2 variants in Parkinson's disease: A comprehensive review

“…[84] Austria 0.00% (162) [68] 0.00% (162) [68] 0.00% (162) [68] 0.00% (162) [68] Morocco 41.00% (100) [118] ---Belgium 0.00% (304) [10] 1.97% (304) [10] 0.00% (304) [10] 0.00% (304) [10] Nigeria 0.00% (183) [119,120] ---Brazil 2.65% (528) [121][122][123][124] 0.00% (154) [125] 0.00% (…”