Genetic vs Environmental Factors That Correlate With Rosacea

Abstract

IMPORTANCE To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions. OBJECTIVES To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility. DESIGN, SETTING, AND PARTICIPANTS Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated. MAIN OUTCOMES AND MEASURESThe NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists. RESULTSAmong the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P < .001) and lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (r = 0.21; P < .001), smoking (r = 0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P < .001). CONCLUSIONS AND RELEVANCEThe study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics

“…The genetics of rosacea are poorly understood. A study in twins suggests a 46% genetic contribution; furthermore, a genomewide association study confirmed that three human leucocyte antigen (HLA) alleles and a small nucleotide polymorphism are genetically linked to rosacea . Interestingly, rosacea‐associated HLA genes have also been identified in other disorders with inflammatory, neural, granulomatous and ocular manifestations …”

Characterization of the facial microbiome in twins discordant for rosacea

“…[1] Previous studies have implicated microbial colonization and the cognate immune response as the critical driver of rosacea. [2,3] Increased levels of Demodex mites and associated bacteria (bacillus), antimicrobial peptides (eg cathelicidin/LL37), host immune variables (eg Tolllike receptor (TLR)-2) and nutrients (eg vitamin D3) are reported to alter the innate immune response and cause chronic inflammation and the facial skin sensitivity in rosacea.…”

“…One of the most important extrinsic ageing factors is sunlight, particularly exposure to ultraviolet (UV) B irradiation, which is a major cause of skin photoageing. [1,2] Exposure of keratinocytes to UVB radiation activates various cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α…”

Association between rosacea severity and relative muscle mass: A cross‐sectional study

“…The association between rosacea and BMI was significant, and weight gain with age and central obesity increased the risk of rosacea . Likewise, a twin study exhibited a positive correlation between rosacea and BMI, ultraviolet radiation exposure and cardiovascular morbidity . Although there were conflicting results among clinical studies, obesity per se may be relevant to rosacea on the basis of a common pathogenesis involving chronic inflammation .…”