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

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