title: The effect of genetic polymorphisms of RARA gene on the adverse effects profile of isotretinoin-treated acne patients.
abstract: OBJECTIVE
  Isotretinoin is a vitamin A-derived medication that is associated with significant adverse effects including arthralgia/ myalgia, nose bleeds, headache, dyslipidemia, liver dysfunction and depression. The mechanism for development of such adverse effects remains elusive, and it is not known why adverse effects develop only in some patients. In this study, we examined the association between rs9303285, rs2715554 and rs4890109 genetic polymorphisms in the retinoic acid receptor alpha (RARA), one of the main targets of isotretinoin, and the adverse effects of oral isotretinoin therapy.
  
  
  METHODS
  Clinical adverse effects data were collected from patient file and by patient interview. Lipids and liver enzymes were measured in blood samples collected from acne patients (n = 300) at baseline and during oral isotretinoin treatment. RARA polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  Three-locus haplotype (Rs2715554 C/T - Rs4890109 G/T - Rs9303285 T/C) analysis showed that frequencies of CTG and TTG haplotypes are significantly associated with occurrence of arthralgia, myalgia, nose bleeds and headache in patients treated with isotretinoin. In addition, TCG haplotype was associated with nose bleeds and headache, whereas TTT haplotype was associated with arthralgia and myalgia. Furthermore, levels of AST were increased, and AST% change was more, after 1 month of treatment in patients with the TC genotype of rs2715554 polymorphism. Finally, allele T of rs9303285 was found to be protective against developing depression in the patients treated with isotretinoin.
  
  
  CONCLUSIONS
  Our findings suggest an association between polymorphisms of RARA gene and some of some common adverse effects of oral isotretinoin.
authors.affiliation: Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan. khalzoubi@just.edu.jo
authors.forename: Karem H
authors.initials: KH
authors.lastname: Alzoubi
authors.forename: Omar F
authors.initials: OF
authors.lastname: Khabour
authors.forename: Razan E
authors.initials: RE
authors.lastname: Hassan
authors.forename: Feras
authors.initials: F
authors.lastname: Qarqaz
authors.forename: Sayer
authors.initials: S
authors.lastname: Al-Azzam
authors.forename: Nizar
authors.initials: N
authors.lastname: Mhaidat
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha
chemical_list: D003879:Dermatologic Agents; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D015474:Isotretinoin