Objective: To investigate relationship between the cyclooxygenase-2 (COX-2) gene promoter region (rs20417, rs689466, rs689465) and 3’untranslated region (rs5275) polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population.

Background: Gene mutation is the most important genetic factor leading to Parkinson’s disease. It provides effective evidence for genetic factors that may play an important role in the progression of some Parkinson’s diseases.Cyclooxygenase is the main speed limiting enzyme in the production of prostaglandin by the metabolism of four arachidic acid. There are at least two homologous isoforms in vivo of cyclooxygenase. The expression of isozyme cyclooxygenase -2 in the substantia nigra region was found to be increased In the autopsy of Parkinson’s disease and in the animal model of Parkinson’s disease . The selective cyclooxygenase -2 inhibitor may become a new drug for Parkinson’s disease.

Methods: A case-control study was conducted in 104 PD patients and 102 healthy volunteers. The total genomes of the peripheral blood samples were extracted. The COX-2 polymorphisms were tested by PCR-restriction fragment length polymorphism (PCR-RFLP), the results were analyzed by c2 test and multiple logistic regression, with the odds ratio (OR) and 95% confidence intervals (CI) to assess the relationship between the factors and the PD risk.

Results: Compared with the control, the -765G>C and -1290G>A genotype and allele frequency distribution in PD group were not found statistically differences. The -1195G>A allele frequency distribution of G and A were statistically significant (P<0.001), the G allele may be more susceptible to PD [dominant model OR=0.33, 95%CI (0.15-0.726), P=0.006]. The 8473T>C allele frequency distribution of T and C were significantly different (P=0.039), the C allele may be associated with the increased PD risk [dominant model OR=2.191, 95%CI (1.092-4.397), P=0.027]. Age stratified analysis showed that the -1195G>A genotypes frequency in the early-onset and late-onset PD group were significantly different compared with the control group (additive model and recessive model, P<0.05); 8473T>C showed an association with late-onset PD (dominant model, P=0.023).

Conclusions: The COX-2 genetic polymorphisms of the -765G>C and -1290G>A loci may not be associated with the susceptibility to PD in the eastern Chinese Han population; -1195G>A and 8473T>C polymorphisms may increase the risk of PD.

References: [1] Yeh NC, Tien KJ, Yang CM, et al．Increased risk of Parkinson’ s disease in patients with obstructive sleep apnea: a population-based, propensity score-matched, longitudinal follow-up study[J]．Medicine (Baltimore), 2016, 95(2) : e2293. [2] Fritz M, Klawonn AM, Nilsson A, et al. Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice [J] . Clin Invest. 2016, 126(2):695-705.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relationship-between-cyclooxygenase-2-gene-polymorphisms-and-parkinsons-disease-susceptibility-in-chinese-han-population/