Epidermiology Of Acne And Its Association With Polymorphisms Of Androgen Receptor Gene

IntroductionAcne is a very common skin disease of adolescence characterized by an inflammation of pilosebaceous follicles.They usually localizes on the face,more often cheeks and forehead,on the chest and back.The most common lesions are comedones, papules and pustules.The major pathogenic factors promoting acne are increased sebum production caused by androgen action,ductal hypercomification,colonization by Propionibacterium acnes,and inflammation.The genetic influence on pathogenesis of acne is well documented in population,twins and genealogic studies in recent years.Along with lives of the people level enhanced,people's life style has also had the huge change,like the rhythm of life speeds up,the mental strain,the sleep reduction as well as the diet to high thermal,the high fat,the high protein transformation and so on, in addition the air environment pollution,the acne disease incidence rate also assumes the tendency which rises year by year,moreover age span fill-out,also has to the youth and the middle-aged development tendency.Androgen play a key role in acne's occurs,development and continuation. Increased sebum production stimulated by androgens is nearly always the first listed pathogenic factor promoting acne.The skin is an important target organ of androgen, many cells in the skin express androgen acceptor(AR),in which sebum gland cell AR expression level are highest,and strengthens along with the cell differentiation. Androgen receptor,a member of the nuclear receptor superfamily,functions as a ligand-dependent transcription factor and is essential for androgen action.The AR gene, located at band q11～12 on the X chromosome,is highly conserved,with germline loss-of-function mutations resulting in androgen insensitivity syndrome,also known as testicular feminization.Three polymorphisms have been identified in the NH2-terminal transactivation domain encoded by exon 1 and include two trinucleotide repeats and a single nucleotide polymorphism.The CAG and less polymorphic GGC repeat lengths have been inversely correlated with protein level and transactivation activity of androgen receptor.The AR-E211 G＞A(rs6152)single nucleotide polymorphism (G1733A)is a synonymous change as the glutamic acid remains unchanged,also known as the StuI or E213 polymorphism,occurring in 13%to 20%of Caucasian populations.It is located between the trinucleotide repeats with which it has been shown to be in partial linkage disequilibrium with both repeats.The research indicated that the polymorphisms of CAG,GGN and AR Stu I in the forst exon of androgen receptor gene are associated with male pattern baldness,prostate cancer and many other diseases.Sawaya et al.studied CAG repeats in androgen related disorders such as acne in American men and women,revealing that shorter CAG repeat lengths were associated with this disorder in both males and females.However,there was no report about the relationship between acne and the polymorphisms of GGN and AR Stu I.Our research first carried out an acne epidemiology investigation in young college students of 5 universities in Shenyang using a cluster-randomized sampling method,to study the prevalence and the risk factors of acne,and try to investigate the genetic influence on pathogenesis of acne from epidemiology angle.Considered the polymorphisms of androgen acceptor gene have different heredity backgrounds in different races,we therefore conducted a case-control study in North East China,to study the AR Stu I polymorphism by polymerase chain reaction-restriction fragment length polymorphisms(PCR-PFLP),and the triplet repeats of CAG and GGN by short tandem repeats(STRs),and try to discussion acne pathogenesis from the molecular genetics angle.Materials and Methods1.Subjects(1)Took 5 universities of Shenyang as the investigation schools,take full-time in the school university undergraduate students as the investigation object,each school according to grade(grade one to grade four,altogether 4 grades)draw 250 students at random,total 5000 students. (2)Acne patient group:238 acne patients,aged 16～37,including 126 males and 112 females(paper 2),522 ache patients,aged 16～39,including 289 males and 233 females(paper 3)were diagnosed in Department of Dermatology,First Hospital of China Medical University,conforms to the Pillsbury diagnosis standard.There were no blood relationships between them.(3)Normal control group:207 examples,aged 16～38,including 109 males and 98 females(paper 2),and 337 examples,aged 16～38,including 156 males and 181 females(paper 3)were random selected as volunteers for health examination.2.Materials10%SDS,EDTA,proteinase K,Tris saturated phenol,chloroform,sodium acetate, alcohol,TE buffer,agarose,DNA polymerase AmpliTaq Gold,2×Taq Plus PCR MasterMix polymerase;Restrictive enzyme StuI3.Methods(1)Using a questionnaire with uniform scheme,a clustered random sampling method was conducted on acne among 5000 young college students in 5 universities of Shenyang.(2)The triplet repeats of CAG and GGN were analyzed by STRs.(3)The polymorphism of AR Stu I was detected by PCR-PFLP.4.Statistical AnalysisAll the statistical analysis of data were performed using the statistical software SPSS(version 13.0),including the Student's t test,Chi-squared test,binary and multiple logistic regression analysis,a two-tailed P＜0.05 was considered to be of statistical significance.To determine whether genotype was in Hardy-Weinberg equilibrium,a x~2 was performed.The genotype frequency and the allele frequency of these genes were compared by x~2,and odds ratio(OR)and 95%confidence interval(CI) indicate the relative risk.Result1.Epidemiology of Acne(1)The total prevalence of ache was 51.3%.Difference in prevalence of acne between males and females showed significant difference(52.75%vs.49.65%;x~2= 4.630,P＜0.031).(2)The risk of ache vulgaris occurring in a relative of a patient with acne vulgaris was significantly greater than for the relative of an unaffected individual(OR:4.68; 95%CI:3.81～5.69;P＜0.001).(3)The age of onset was 16.24±2.32 years in the cases with positive family history and 16.67±2.31 years without family history.There is significant difference between them(F=0.059,P＜0.001).(4)The risk factors of acne are:family history,mental strain,menstrual disorder, lose sleep frequently,Pungent food,male,menorrhalgia,anxious,sleep less than 8 hours everyday,depression,fry explode food,higher study pressure,greasy food,oily skin,mixing property skin,among them,the OR of family history(4.695)is the highest; The protective factors are:dry skin,neutral skin,eat fruit frequently,Operate the computer a short time everyday.2.Association of CAG and GGN repeats in the first exon of androgen receptor gene and acne risk.(1)Men with fewer than 23 CAG repeats had a OR for acne of 2.07(OR:2.07; 95%CI:1.21-3.54;P=0.008)compared to men with longer repeat length.(2)Women with fewer than 24 CAG repeats also had an OR for acne of 2.05(OR: 2.05;95%CI:1.18-3.56;P=0.013)compared to women with longer repeat length.(3)Men with CAG＜23/GGN≤23(OR:3.33;95%CI:1.10-10.07;P＜0.05)had an increased risk compared to men with CAG≥23/GGN＞23.3.Association of genetic polymorphisms in the androgen receptor gene AR Stu I with acne.(1)The allele frequencies of AR Stu I G/A was in Hardy-Weinberg equilibrium in acne cases and in controls.(2)Significant difference was observed between the male acne patients and male healthy controls in the distribution allelic frequencies of the AR Stu I polymorphism (OR:2.64;95%CI:1.22-5.73;P=0.01).(3)Significant difference were observed between the female acne patients and female healthy controls in the distribution allelic(OR:2.13;95%CI:1.18-3.84;P=0.01) and genotypic frequencies(OR:1.97;95%CI:1.02-3.79;P=0.04)of the AR Stu I polymorphism.Conclusion1.Acne is one of the common diseases in college students in Shenyang.2.Male,mental strain,anxious,depression,higher study pressure,Pungent food, greasy food,fry explode food,menstrual disorder,menorrhalgia,sleep less than 8 hours everyday,lose sleep frequently,oily skin,mixing property skin and family history are risk factors for ache;Eat fruit frequently,operate the computer less than 2 hours everyday,dry skin,and neutral skin are protective factors for acne.3.The risk of acne occurring in a relative of a patient with acne was significantly greater than for the relative of an unaffected individual.Patients with positive family history had an earlier age of onset,suggests that familial factors are important in determining individual susceptibility to acne.4.Shorter CAG repeat lengths were associated with ache in both males and females.5.GGN repeats,considered independently of the CAG repeat,have no evident effect on acne risk,but short GGN repeats increase even further the risk of acne in men bearing short CAG repeats.6.The CAG and GGN repeat lengths of exon 1 in androgen receptor gene could serve as susceptibility marker for ache in North East China.7.The AR Stu I A allele is associated with a lower risk of acne in both male and female in in North East China.