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Kangni Zheng, MD; Bobak Heydari, BS; David K. Simon, MD, PhD

Arch Neurol. 2003;60:722-725.

Background  NURR1 plays a key role in mesencephalic dopaminergic neuron development and survival. A homozygous NURR1 polymorphism (a single base-pair insertion in intron 6) (NI6P) has been reported to be associated with Parkinson disease (PD).

Objective  To assess the association of the NI6P with PD and diffuse Lewy body disease.

Design  Case-control study.

Setting  Movement disorders clinic and tissue provided by brain banks.

Patients  Patients with pathologically proven PD (n = 37) or diffuse Lewy body disease (n = 35), neuropathologically normal control subjects (n = 59), those clinically diagnosed as having PD (n = 66), and spousal controls (n = 29).

Methods  Determining the frequency of heterozygotes and homozygotes for the NI6P by DNA sequencing and restriction endonuclease analyses.

Results  Overall, 41 (39.8%) of the 103 patients with PD were heterozygotes compared with 22 (25.0%) of the 88 controls (P = .03), with a relative risk (estimated from the odds ratio) for PD of 2.03 (95% confidence interval, 1.08-3.81) for heterozygotes vs wild type subjects. Heterozygotes were more frequent in the subgroup of patients with pathologically confirmed PD (18 [48.6%] of 37) vs controls (14 [23.7%] of 59) (P = .01), with a relative risk for PD of 2.84 (95% confidence interval, 1.17-6.88) for heterozygotes vs wild type subjects. In patients clinically diagnosed as having PD, heterozygotes were more frequent in early-onset cases (onset at 45 years) (10 [55.6%] of 18) compared with late-onset cases (onset at >45 years) (10 [23.8%] of 42) (P = .02) or spousal controls (8 [27.6%] of 29) (P = .06), with a relative risk for early-onset PD of 4.17 (95% confidence interval, 1.13-15.33) for heterozygotes vs subjects with 2 wild type alleles. The homozygous NI6P was not associated with PD, but was present in 6 (17.1%) of the 35 patients with diffuse Lewy body disease compared with 3 (5.1%) of the 59 controls (P = .06).

Conclusions  The common heterozygous NI6P is associated with an increased risk of PD. An association of borderline significance was found for the homozygous NI6P and diffuse Lewy body disease.

From the Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

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