Introduction:
The high rate of multiple sclerosis (MS) in the Gorski Kotar Region of Croatia is currently unexplained. This is the only region in Croatia with an average yearly temperature below 9°C. Colder temperatures corresponds to the immune system regulator TRPM8.

Aim:
To determine if average yearly temperature is associated with MS prevalence rates in Croatia and what average yearly temperature is the most significantly associated when variation is considered.

Material and methods:
Weather data from the Croatian Meteorological and Hydrological Service was compared to MS prevalence rates from 28 locations in Croatia. Multivariate analysis was used to determine the significance of a correlation between average yearly temperature and MS prevalence. When this was determined the same method was repeated with variation towards a particular temperature.

Results and discussion:
The results were significant for all areas combined (P < 0.013) and were highly significant in non-coastal areas (P < 0.002) but not significant in coastal areas (P < 0.44). 10.87°C was found to be the most significantly associated temperature (P < 1.60 × 10–4) and variation was found to be significantly associated (P < 0.05) between 7.9°C and 8.29°C. Swimming can have the same effects on the body as colder weather and this could explain the lack of association in coastal areas. MS prevalence rates also shows corresponding metrics with specific cancers which are known to be linked to the TRPM8 receptor.

Conclusions:
MS prevalence in Croatia is significantly associated with average yearly temperature. MS also has the highest prevalence rates in areas which correspond to peak activity of the TRPM8 receptor.