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Finasteride is not necessarily effective on all of the male pattern baldness (MPB) patients. To know any factor which correlates with the effectiveness of finasteride, the polymorphism of androgen receptor (AR) gene was analyzed. Symptoms of the 488 MPB patients (18–62 y) before and after treatment with total dose of 10 mg or more of finasteride was typed by photographic method. The number of CAG and GGC repeats in AR gene of MPB patients was determined by DNA sequencing. When the number of the triplet repeats (CAG+GGC) was plotted against the degree of symptom improvement after treatment with this drug, a broad correlation between these variables was observed. The smaller the repeat number, the higher the improvement with finasteride. The group of patients with shorter repeat region in AR gene responded better to this drug than that with longer repeat region, although the former patients tended to reveal severe initial symptoms. Determination of such polymorphism is thought to be useful in the drug choice for MPB patients.
Most male pattern baldness (MPB) patients have an androgen-dependent trait, although it is thought to be under the control of multiple genes, such as genes for androgen receptor (AR), insulin-like growth factor-1 (IGF-1), and dihydrotestosterone regulations (
The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia.
). One of the 5 α-reductase inhibitors, finasteride, is effective on MPB, although there is a variation in the efficacy of this drug among the MPB patients. From the functional mechanism of this drug, it is thought to be effective on the MPB caused by hyperfunction of AR. Association of higher incidence rate of MPB with lower triplet repeat number in the first exon of AR gene has been demonstrated by some authors (
Wakisaka et al, The 11th Annual Meeting of the SHSR jointly with KHRS 2003.
To investigate the relationship between the effectiveness of finasteride and the AR gene polymorphism, we determined the number of triplet repeats in AR gene of patients.
Results and Discussion
Effectiveness of finasteride on each patient was expressed as the improvement point of symptom derived from the modified Hamilton–Norwood typing. The number of the triplet repeats (CAG+GGC) was plotted against the symptom points. There was a broad correlation between these variables Figure 1. The smaller the repeat number, the higher the improvement with finasteride. Patients were divided into two groups: the group comprised of patients whose number of repeats was 40 or less, and the group of more than 40. Larger number of patients in the former group (≤40) obtained higher improvement points, compared with that in the latter (>40) (data not shown). Finasteride was more effective on patients in the short repeat group (≤40); even they had severe initial symptoms (V–VII). The relation between the improvement points and total dose of fnasteride was analyzed. In the shorter repeat group (≤40), their mean improvement point was 0.96 to 1.1 even by a smaller total dose, 30–100 mg, while 200 mg or more was necessary to achieve the same improvement in the long repeat group (>40). Finasteride was less effective on patients in the long repeat group (>40) especially on patients younger than 30 y.
Figure 1Effect of finasteride on patients with different triplet repeat numbers in androgen receptor (AR) gene. Vertical column, mean improvement points; Broken line, regression line of mean improvement points; vertical bars, SD of mean.
As mentioned above, we have found that the shorter the CAG and GGC repeat numbers, the higher the symptom level before treatment with finasteride. Although, the mean initial symptom of patients in the short repeat group was worse, finasteride was more effective in the improvement of MPB in most patients with shorter triplet regions of AR gene. These cases may be caused by hyperfunction of AR. On the other hand, this drug was less effective in certain cases with longer triplet repeats. They are thought to result from a non-androgenic mechanism. This kind of analysis may aid in the choice of drug for MPB patients.
Materials and Methods
Symptoms were typed by a single judge, independent of clinicians, from photography of patients according to the Hamilton–Norwood typing, to which II-v was added (modified H–N typing). For statistical analysis, the symptom types of I–VII were converted to numerical values, 1–9. We selected 488 MPB patients (18–62 y), who received 0.2 to 1.0 mg of finasteride daily for 20 d or longer (the total dose was 10 mg or more). Patients with initial symptoms of II or lower were omitted to observe a reliable effect of the drug. DNA was extracted from blood cells. After PCR of the first exon of AR gene, the number of CAG and GGC triplets was determined by conventional sequencing (Sanger's method). DNA containing the long GGC repeat region (>22 repeats), however, were sequenced by the transcriptional sequencing method (
The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia.
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