Research On Relationship Of Depressed Liver-dispersing And Liver Fire-purging Therapy And Polycystic Ovary Syndrome In Patients With Syndrome Of Liver Excessive Heat With The Polymorphism Of CYP11B2/CYP17 Gene

Objective: Polycystic ovary syndrome (PCOS), one of the most common endocrinediseases affecting women of reproductive age, plays an important role in anovulatoryinfertility. PCOS is the endocrine syndrome of plenty pathogeny and clinical manifestationspolymorphism. Up to now, precise pathogenesy of PCOS is yet unknown. Observation ofmany years discovered that strong familial aggregation of PCOS patients compatriots insisters. The incidence rate of PCOS increased to over 40%, which suggested that geneticfactors in the pathogenesis play a very critical role.After many years of clinical observation, Prof. Zhang discovered that a considerablenumber of PCOS patients, especially the younger patientS were caused by stagnation ofliver-QI, hepatic fire except for kidney deficiency, phlegm and blood stasis. Preliminarystudy found that the important clinical and biochemical features of hepatic fire in PCOSwere hyperandrogenism, Depressed liver-dispersing and heat fire-purging therapy was asignificant therapeutic principle, Modifying Longdan Xiegan Prescription hadpredominant clinical therapeutic effect.TCM syndrome is a relatively stable pathophysiological state. The formation of suchpathophysiological state is related with the quality of genetic susceptibility, determined bythe individual genes. The genetic characteristics determined by individual gene are materialbasis of TCM syndrome. For a long time, the susceptibility of different individuals of thesame disease is different on the clinical recognition. And with the same disease of differentindividuals, its clinical manifestations and response to treatment and prognosis aresignificantly different. Now, the human genome polymorphism play an important role inarticulating of human disease, drug sensitivity and tolerance, clinical manifestations ofdisease diversity and the treatment responses. Documents showed CYP11B2/CYP17 genepolymorphism were related with hyperandrogenism of PCOS. Research on relationship ofdepressed liver-dispersing and liver fire-purging therapy and PCOS patients with syndromeof excessive liver heat with the polymorphism of CYP11B2/CYP17 gene could revealmolecular and genetic mechanism of depressed liver-dispersing and liver fire-purging therapy and syndrome of excessive and stagnant heat liver meridian of the patients withPCOS further, which could guide clinical therapy and be of great significance.Methods: In clinical research, 74 patients which were consistent with our study standardwere divided into two groups: group TCM of excessive and stagnant heat in liver meridian(42 cases), treated with depressed liver-dispersing and liver fire-purging Prescription(Modifying Longdan Xiegan Prescription), one dose every day, for 3 months; group TCMof kidney deficiency(32 cases), and choose the same period due to tubal factor infertility in27 patients as the control group. The information, such as pattern of their menstruation,acne, hairness, and so on, was collected. On the same time, the levels in serum of LH, FSH,FT, A, T were assayed. The DNA of 74 patients with PCOS and 27 controls were detectedfor the substitution of T→C at-34 bp in CYP17 gene and the substitution of T→C at-344in CYP11B2 gene by using polymerase chain reaction and restriction fragment lengthpolymorphism (PCR—RFLP). The relationship of CYP11B2/CYP17 potymorphism andserum T,FT,A levels between three groups was analyzed.Results: 1. Group TCM of excessive and stagnant heat in liver meridian have higher LH,LH/FSH value and more acne patients than the group of TCM kidney deficiency, thedifference was significant (P＜0.05). After treatment, five cases infertility were pregnant,Irregular menstruation, acne, irritable irritability, breast pain, chest tightness, were allimproved significantly in group TCM of excessive and stagnant heat in liver meridian(P＜0.05); The levels of LH, LH/FSH, T, FT, A in group TCM of excessive and stagnantheat in liver meridian were all obviously lower than those of pre-therapy (all P＜0.05).2. The prevalence rate of CYP11B2 genotype CC+TC were 48.64% in PCOS and40.74% in control group, respectively. The frequencies of CYP11B2 C alleles were26.35 %, in PCOS group and 22.22 % in control group respectively. Neither the genotypedistributions nor the allele frequencies were significantly different between PCOS groupand control group. The genotype distributions was not significantly different between groupTCM of excessive and stagnant heat in liver meridian and group TCM of kidneydeficiency. Analysis on relationship between gene type and depressed liver-dispersing andliver fire-purging therapy, the therapy were effective to patients in group TCM of excessiveand stagnant heat in liver meridian of different gene types. The effect was similar in spite ofwhat gene types the patients with.3. The prevalence rate of CYP17 genotype CC were 52.70% in PCOS and 29.63% incontrol group, respectively. The frequencies of CYP17 C alleles were 72.11%, in PCOSgroup and 55.56% in control group respectively. Both the genotype distributions and theallele frequencies were significantly different between PCOS group and the control group. The testosterone levels in the CC subgroup of PCOS group were significantly higherthan that of and TC TT subgroup. The prevalence rate of CYP17 genotype CC, TC were34.38%, 56.25% in Group TCM of kidney deficiency and 66.67%,26.19% in group TCMof excessive and stagnant heat in liver meridian, respectively, the genotype distributionswas significantly different between group TCM of excessive and stagnant heat in livermeridian and group TCM of kidney deficiency. The testosterone levels in the CC subgroupof Group TCM of excessive and stagnant heat in liver meridian were significantly higherthan that of and TC, TT subgroup. Analysis on relationship between gene type anddepressed liver-dispersing and liver fire-purging therapy, therapy were effective to patientsgroup TCM of excessive and stagnant heat in liver meridian of different gene types. Theeffect of either was similar in spite of what gene types the patients with.Conclusion: 1. Excessive heat of the liver was one of the most important pathogenesisin PCOS. The important biochemical features of excessive liver heat in PCOS serum werehigher levels of LH, LH/FSH than that of kidney deficiency group.2. Depressed liver-dispersing and liver fire-purging therapy was a significant therapeuticprinciple, Modifying Longdan Xiegan Prescription had predominant clinical therapeuticeffect; It could effectively decrease the serum of T, FT, A, and could ameliorate the majorclinical symptoms.3. The substitution of-344 T of CYP11B2 gene might not be correlated with PCOS,and may not be one of the susceptive genes of PCOS. CC gene type is not related tosyndrome of excessive heat of the liver in PCOS. The effect of depressed liver-dispersingand liver fire-purging therapy was not related to whether C allele was borne.4. The substitution of -34 bp(T/C)of CYP17 gene might be correlated with the hightestosterone level of PCOS, and may be one of the susceptive genes of PCOS. CC genetype is related to syndrome Of excessive heat of the liver in PCOS. The effect of depressedliver-dispersing and liver fire-purging therapy was not related to whether C allele wasborne.