Genetic Factors and Immunological Determinism of Persistent Consequences of Chikungunya

Chikungunya virus (CHIKV) infection has become a threat to public health worldwide. Reunion Island, due to the 2005-2006 epidemic, has acquired unique expertise and remains at the forefront of global research on this disease. The idea of genetic determinism of the clinical expression of infectious diseases has been supported by many epidemiological arguments over the past fifty years. The identification of genetic variants, associated with a disease, often allows a better understanding of the molecular mechanisms involved with consequent significant benefits such as the development of specific biomarkers for new preventive (vaccination) and / or therapeutic (drug design) approaches. In the absence of well-documented hypotheses about the genes potentially involved in the occurrence or evolution of a disease, genome-wide association studies (GWAS), whole genome, of nucleotide polymorphisms (SNPs) and the principle of linkage disequilibrium, under the commonly accepted hypothesis that the expression of a common disease is based on a small number of alleles commonly found in the population (frequency of minor allele greater than 1-5%), have become a method of choice, free of hypothesis, to specify the part of heritability of a complex disease and to identify its genetic determinants. Several epidemiological arguments support a significant proportion of genetic determinism in the explanation of the evolutionary pattern of Chikungunya, whose proportion of chronic forms can reach 40-60% in population-based studies conducted in the two years following an epidemic:

• There are few risk factors associated with chronic forms and these appear to be unclear (age, comorbidities with several elements of the metabolic syndrome) or inconsistent (immune burden) in population studies;
• The incidence of severe or atypical forms is rare in the order of 1% of infections;
• In contrast to the acute phase (J1-J21) for which there seems to be a role of the viral load intensity and a consensual pro-inflammatory immune signature according to a recent meta-analysis]; The role of the intensity of the viral load in the pathogenesis of chronic arthralgia (> J90) and their immune signature remain to be determined, the latter being rather nonspecific, according to studies conducted in Reunion, Italy or Singapore.

These elements justify the interest of a GWAS in the Chikungunya to identify new avenues and mechanistic hypotheses likely to explain the chronic arthralgia characteristic of the disease.