Footprints of Stress in Vitiligo: Association of the 5-HTR2C rs6318 Variant

Vitiligo is a chronic, progressive autoimmune dermatological disease, and stress is known to have an impact on the development of vitiligo. However, the effect of the serotonin pathway and its impact have not been clearly explained for disease progression. Thus, this study aimed to clarify the stress induced serotonin receptor 5-HTR2C rs6318 variant and its association with vitiligo pathogenesis.

Case-control study was conducted with 108 vitiligo patients and 107 age-sex matched, unrelated healthy control group. Real Time-PCR analysis was used for genotyping the 5-HTR2C variation. Genotype and allele frequencies, genotype distributions, Hardy-Weinberg Equilibrium (HWE) and vitiligo-related risk measurements were examined. Genotype correlations of the variant were also analyzed based on gender difference, age onset, Koebner phenomenon history, triggered with stress, clinical subgroups, treatment types, the presence of other autoimmune diseases, vitiligo presence in family members and other auto-immune diseases in relatives.

Statistical differences in 5HT-R2C receptor genotypes and allele frequencies between patients and controls were not detected. Genotype frequencies were not in agreement with Hardy-Weinberg Equilibrium in the patients’ group (p<0.00001). The frequency of the risk allele (allele C) was not significantly different between the patient and control groups (p=0.1392). However, in the clinical subgroup analysis, the risk allele presence was detected to be significantly higher for early age onset (<40 years) vitiligo development (p=0.035, OR=Infinity, RR=1.391) and lower in Koebner phenomenon history (p=0.0276, OR= 0.219, RR=0.325).

In conclusion, although there was no association between the 5-HTR2C variant rs6318 and vitiligo, current results indicate that there is an association between the 5HTR2C rs6318 variant C allele and early onset vitiligo development.