Genetic Determinants of Hair Color and Parkinson's Disease Risk

Overview

Journal Ann Neurol

Specialty Neurology

Date 2009 Feb 6

PMID 19194882

Citations 56

Authors

Xiang Gao

Kelly C Simon

Jiali Han

Michael A Schwarzschild

Alberto Ascherio

Affiliations

Soon will be listed here.

Abstract

Objective: A history of melanoma is associated with increased risks for Parkinson's disease (PD). We examined whether hair color, one of the most important phenotypes of pigmentation and a risk factor for melanoma, was associated with PD risk in the Health Professionals Follow-up Study (HPFS; 1986-2002) and the Nurses' Health Study (NHS; 1980-2002).

Methods: We included 38,641 men and 93,661 women who were free of PD at baseline. Information on natural hair color in early adulthood (age 18-21 years) was assessed via a questionnaire. We also conducted a case-control study (298 PD cases) nested in these two cohorts to examine the association between the melanocortin1-receptor Arg151Cys polymorphism and PD risk. Relative risks (RRs) were estimated using Cox proportional hazards models in the cohort analyses and conditional logistic regression in the nested case-control study.

Results: PD risk increased with decreasing darkness of hair color. Pooled RRs for PD were 1 (reference), 1.40, 1.61, and 1.93 (95% confidence interval, 1.1-3.4) for black, brown, blond, and red hair, respectively, after adjusting for age, smoking, ethnicity, and other covariates. The associations between hair color and PD were particularly strong for relative younger onset of PD (<70 yr) (adjusted RR for red vs black hair = 3.83; 95% confidence interval, 1.7-8.7). In the case-control study, participants with Cys/Cys genotype, which was associated with red hair, had a greater PD risk, relative to the Arg/Arg genotype (adjusted RR, 3.15; 95% confidence interval, 1.1-9.4).

Interpretation: These findings suggest a potential role of pigmentation in PD.

Citing Articles

Hair color, family history of melanoma, and the risk of Parkinson's disease: An analysis update.

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Parkinson Disease Genetics Extended to African and Hispanic Ancestries in the VA Million Veteran Program.

Pankratz N, Cole B, Beutel K, Liao K, Ashe J Neurol Genet. 2023; 10(1):e200110.

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Racial and Ethnic Disparities in Parkinson Disease: A Call to Action.

Aamodt W, Willis A, Dahodwala N Neurol Clin Pract. 2023; 13(2):e200138.

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Chemiexcitation: Mammalian Photochemistry in the Dark.

Brash D, Goncalves L Photochem Photobiol. 2023; 99(2):251-276.

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Redheaded women are more sexually active than other women, but it is probably due to their suitors.

Sykorova K, Fiala V, Hlavacova J, Kankova S, Flegr J Front Psychol. 2022; 13:1000753.

PMID: 36524175 PMC: 9746287. DOI: 10.3389/fpsyg.2022.1000753.

References

Ferreira J, Silva J, Freire R, Pignatelli J, Guedes L, Feijo A . Skin cancers and precancerous lesions in Parkinson's disease patients. Mov Disord. 2007; 22(10):1471-1475. DOI: 10.1002/mds.21575. View

Berlin J, Longnecker M, Greenland S . Meta-analysis of epidemiologic dose-response data. Epidemiology. 1993; 4(3):218-28. DOI: 10.1097/00001648-199305000-00005. View

van der Velden P, Sandkuijl L, Bergman W, Pavel S, van Mourik L, Frants R . Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma. Am J Hum Genet. 2001; 69(4):774-9. PMC: 1226063. DOI: 10.1086/323411. View

Chen H, OReilly E, Schwarzschild M, Ascherio A . Peripheral inflammatory biomarkers and risk of Parkinson's disease. Am J Epidemiol. 2007; 167(1):90-5. DOI: 10.1093/aje/kwm260. View

Jansson B, Jankovic J . Low cancer rates among patients with Parkinson's disease. Ann Neurol. 1985; 17(5):505-9. DOI: 10.1002/ana.410170514. View

Gao X, Chen H, Schwarzschild M, Glasser D, Logroscino G, Rimm E . Erectile function and risk of Parkinson's disease. Am J Epidemiol. 2007; 166(12):1446-50. PMC: 2385785. DOI: 10.1093/aje/kwm246. View

Han J, Kraft P, Colditz G, Wong J, Hunter D . Melanocortin 1 receptor variants and skin cancer risk. Int J Cancer. 2006; 119(8):1976-84. DOI: 10.1002/ijc.22074. View

Catania A, Gatti S, Colombo G, Lipton J . Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004; 56(1):1-29. DOI: 10.1124/pr.56.1.1. View

Lerner M, Goldman R . Skin colour, MPTP, and Parkinson's disease. Lancet. 1987; 2(8552):212. DOI: 10.1016/s0140-6736(87)90786-0. View

10.

Forslin Aronsson S, Spulber S, Popescu L, Winblad B, Post C, Oprica M . alpha-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia. Neuropeptides. 2006; 40(1):65-75. DOI: 10.1016/j.npep.2005.10.006. View

11.

Zecca L, Tampellini D, Gerlach M, Riederer P, Fariello R, Sulzer D . Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. Mol Pathol. 2001; 54(6):414-8. PMC: 1187132. View

12.

Box N, Duffy D, IRVING R, Russell A, Chen W, Griffyths L . Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol. 2001; 116(2):224-9. DOI: 10.1046/j.1523-1747.2001.01224.x. View

13.

Gao X, Chen H, Choi H, Curhan G, Schwarzschild M, Ascherio A . Diet, urate, and Parkinson's disease risk in men. Am J Epidemiol. 2008; 167(7):831-8. PMC: 2367211. DOI: 10.1093/aje/kwm385. View

14.

Gasser T . Genetics of Parkinson's disease. J Neurol. 2001; 248(10):833-40. DOI: 10.1007/s004150170066. View

15.

Zhang L, Dawson V, Dawson T . Role of nitric oxide in Parkinson's disease. Pharmacol Ther. 2005; 109(1-2):33-41. DOI: 10.1016/j.pharmthera.2005.05.007. View

16.

Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W . Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol. 2001; 117(2):294-300. DOI: 10.1046/j.0022-202x.2001.01421.x. View

17.

Palmer J, Duffy D, Box N, Aitken J, OGorman L, Green A . Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?. Am J Hum Genet. 2000; 66(1):176-86. PMC: 1288324. DOI: 10.1086/302711. View

18.

Van Den Eeden S, Tanner C, Bernstein A, Fross R, Leimpeter A, Bloch D . Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003; 157(11):1015-22. DOI: 10.1093/aje/kwg068. View

19.

Schaffer J, Bolognia J . The melanocortin-1 receptor: red hair and beyond. Arch Dermatol. 2001; 137(11):1477-85. DOI: 10.1001/archderm.137.11.1477. View

20.

Tan L, Venketasubramanian N, Jamora R, Heng D . Incidence of Parkinson's disease in Singapore. Parkinsonism Relat Disord. 2006; 13(1):40-3. DOI: 10.1016/j.parkreldis.2006.07.003. View