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    1 Comment for this article
    Increased maternal relationships among MS patients may be due to greater female than male fertility
    Steven R Brenner, MD | Dept. Neurology St. Louis VA & Dept. Neurology & Psychiatry at St. Louis University
    I read with interest the article on maternal transmission of Multiple Sclerosis (MS) in a Dutch population by Hoppenbrouwers.(1) The reason for the higher maternal relationship between MS patients may indicate a higher potential for parenthood or fertility in females than males with MS, resulting in fewer offspring in males than females. Over the extended generations in the genetically isolated population, this would result in a higher maternal than paternal relationship among the MS patients in the study.
    In women with multiple sclerosis, the rate of relapses declines during pregnancy,(2) which could result in less disability among women
    than men, making them more likely to bear children, and there could possibility be additional benefits on potential fertility from additional pregnancies.
    Vitamin D3 may have a greater protective effect in females than males against development of MS as well, since Vitamin D3 offered protection from autoimmune encephalomyelitis only in female mice, and not male or ovarietomized female mice.(3) If such a protective effect in females with MS from vitamin D is present in humans with MS, as is present in mice with experimental autoimmune encephalomyelitis, it could cause less disability and perhaps explain greater fertility in females than males with increased offspring in females.
    The tendency for mothers to be more closely related than fathers of MS patients in the isolated Dutch population may indicate a greater potential for childbearing among females than males with MS over extended generations.
    1. Hoppenbrouwers I A, Liu F, Aulchenko Y S, et al. Maternal transmission of multiple sclerosis in a Dutch Population. Arch Neurol.2008;65:345-348
    2. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med.1998;339:285-291.
    3. Spach KM, Hayes C, Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol.2005;175:4119-4126.
    No relevant financial interests.
    Original Contribution
    March 2008

    Maternal Transmission of Multiple Sclerosis in a Dutch Population

    Author Affiliations

    Author Affiliations: Department of Neurology, MS Centre Erasms (Drs Hoppenbrouwers and Hintzen), Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics (Drs Liu, Aulchenko, and van Duijn), and Department of Clinical Genetics (Dr Oostra), Erasmus MC, Rotterdam, the Netherlands; and Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford, Oxford, England (Dr Ebers).

    Arch Neurol. 2008;65(3):345-348. doi:10.1001/archneurol.2007.63

    Objective  To investigate the parental relationship of patients with multiple sclerosis (MS) from an extended pedigree with extensive genealogical information up to the middle of the 18th century.

    Design  Multiple sclerosis is a complex disease resulting from genetic and environmental factors. Parent-of-origin effect, a phenomenon when the same allele may express differently depending on the sex of the transmitting parent, may influence the risk for MS. We investigated parental relationships between patients with MS using extensive genealogical information available from the Genetic Research in Isolated Populations program. We compared the average kinship of the parents of MS patients. We further explored the distribution of shortest genealogical links between parents of MS patients.

    Subjects  Twenty-four MS patients from the isolated population who could be linked within a large complex pedigree, including 2471 people in total.

    Results  The results consistently indicate a higher prevalence of maternal transmission of MS. The kinship between mothers of patients was 3.8 times higher than that between fathers (bootstrap P = .01). Among the 814 shortest connections between parents, 333 were maternal (40.9%, vs 25.0% expected), 98 were paternal (12.0%, vs 25.0% expected), and 383 were maternal-paternal (47.1%, vs 50.0% expected) (P < .001).

    Conclusions  Mothers of MS patients were more closely related than their fathers. This skewed relationship shows evidence for a maternal effect in MS. The most likely explanation is a gene-environment effect that takes place in utero.