Association of HLA locus variant in Parkinson's disease

Abstract

A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

“…The rs3129882 variant was replicated in Han Chinese from mainland China [226]. Surprisingly, however, the rs3129882 variant was found to be inversely associated with PD risk in ethnic Chinese populations from South Asia [227]. This possibly underscores the polymorphic heterogeneity of the HLA region even amongst populations with seemingly recent common ancestry.…”

HLA-DRArs3129882 A/G polymorphism was not a risk factor for Parkinson's disease in Chinese-based populations: a meta-analysis

“…However, Chiang and Lin could not replicate the relationship between rs3129882 polymorphism and PD risk in Taiwan populations [15,16]. Interestingly, another study based on ethnic Chinese populations from Singapore and Malaysia showed an association of A allele with deceased risk of PD [13].…”

“…However, this association was not detected in other case-control studies using samples from Taiwan [15,16]. Recently, a study based on ethnic Chinese subjects in Singapore and Malaysia showed that the minor A allele of HLA-DRA is associated with a decreased susceptibility of PD [13]. Considering published data are contradictory, the association of HLA-DRA rs3129882 A/G polymorphism with PD is still inconclusive.…”

“…Controls were selected from healthy individuals matched on age and gender. There are two studies from Mainland China [12,14], two studies from Taiwan [15,16], and one study from Singapore and Malaysia [13]. The genotype testing methods included polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and TaqMan assay.…”

“…Interestingly, studies of Caucasian cohorts found the G allele to be a susceptibility allele [8,9], while the minor A allele was reported to be a susceptibility allele in Chinese-based populations [12][13][14]. However, even in Chinese-based populations, the association between variants in HLA-DRA and PD has been controversial.…”