This Article Full Text (PDF) All Versions of this Article: 1352458509106745v1 15/9/1030    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Cocco, E Articles by Marrosu, M. PubMed PubMed Citation Articles by Cocco, E Articles by Marrosu, M. Social Bookmarking                         What's this?

Multiple sclerosis risk: interaction between human leukocyte antigen and the environment in Sardinian population

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italy

C Sardu

Dipartimento di Sanità Pubblica, Università di Cagliari, Italy

R Murru

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italy

J Frau

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italy

L Lorefice

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italy

E Mamusa

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italy

P Contu

Dipartimento di Sanità Pubblica, Università di Cagliari, Italy

MG Marrosu

Centro Sclerosi Multipla, Dipartimento di Scienze Cardiovascolari e Neurologiche, Università di Cagliari, Italygmarrosu{at}unica.it

Background

The island of Sardinia features a high incidence of multiple sclerosis (MS) characterized by early age at onset and a progressively increasing trend. The current study was aimed at examining variations in human leukocyte antigen–risk genotypes occurring over time in a cohort of patients.

Methods

Susceptible and neutral DRB1-DQB1 genotypes were identified in 1660 patients. Age at onset was established in 1436 patients divided into two cohorts, an older cohort (subjects born before 1949, N = 233) and a younger one (subjects born from 1960 to 1989, N = 850). Patients from the older cohort were randomly assigned to patients of the same sex from the younger cohort, matched for age at onset. The final sample included 170 pairs. Logistic conditional analysis was performed to determine the probability of a neutral genotype in both cohorts. Kaplan–Meier analysis was applied to ascertain the influence of predisposing and neutral genotypes in age at onset for both cohorts.

Findings

The probability of carrying a neutral genotype was 1.76-fold higher in the younger than in the older cohort (P = 0.02) and 3.67-fold higher in men (P = 0.005). Kaplan–Meier analysis revealed an earlier age at onset in patients of the young cohort carrying the predisposing genotype (P = 0.004).

Interpretation

In the Sardinian population, an environment more prone and propitious to autoimmunity may contribute toward the rising incidence of MS or anticipate overt manifestation of the disease in genetically predisposed subjects.

Key Words: environment • genes • HLA • multiple sclerosis

This version was published on September 1, 2009

Multiple Sclerosis, Vol. 15, No. 9, 1030-1036 (2009)
DOI: 10.1177/1352458509106745


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?