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Background Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. Objectives We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. Methods Among participants of the community‐based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. Results We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0·008). The TT/tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT/tt genotype had about a sevenfold increase, whereas fair‐skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT/tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair‐skinned people with VDR‐Apa AA/aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. Conclusions The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.  相似文献   

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Vitiligo is a multifactorial skin disease with established role of genetics and autoimmunity in its pathogenesis. Vitamin D receptor (VDR) polymorphisms have been suggested to correlate with risk of vitiligo in some ethnic populations. On the other hand, cathelicidin, one of the innate immune system components, has a role in development of some chronic skin diseases and VDR regulates the expression of cathelicidin. We aimed to determine the plasma level of cathelicidin and its association with the VDR gene polymorphisms as well as plasma vitamin D level in patients with vitiligo. Ninety vitiligo patients and 90 non-vitiligo controls participated in this study. Blood levels of 25(OH) vitamin D and cathelicidin were determined with ELISA. Genotyping for VDR polymorphisms (ApaI, TaqI, FokI and BsmI) was done with RFLP-PCR method. Mean blood level of cathelicidin was significantly higher in vitiligo patients as compared to controls (P < .0001). Mean blood level of vitamin D was significantly lower in patients than controls (P = .01). Statistically significant differences were not observed for both genotype and allele frequencies of BsmI, ApaI and TaqI polymorphisms. There was a borderline increased risk of vitiligo in over-dominant model of FokI polymorphism with OR = 1.8 and P = .051. Our findings was suggestive of the potential role of cathelicidin in the pathogenesis of vitiligo; however, future evaluations are needed to determine its precise mechanism. Genetic study of VDR gene polymorphism was suggestive of increased risk of vitiligo in association with a FokI polymorphism in Iranian population.  相似文献   

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AIM: To investigate the effects of different methylenetetrahydrofolate reductase(MTHFR) 677CT gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial.METHODS: We challenged the relationship, if any, of MTHFR 677CT and MTHFR 1298AC polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677 T and A1298 C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677 T is present independently of the negative effects of left ventricular hypertrophy, increased IntraRenal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.  相似文献   

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BACKGROUND: Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. OBJECTIVES: The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. METHODS: One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. RESULTS: All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. CONCLUSIONS: Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.  相似文献   

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Background

Vitamin D receptor (VDR) polymorphisms may play an important role in the vitiligo susceptibility. There have been many studies looking at the associations between VDR polymorphisms and vitiligo risk, but the conclusions are still up for debate.

Aim

This study aimed to determine whether polymorphisms in the VDR are associated to the susceptibility to vitiligo.

Methods

Vitamin D receptor polymorphisms in vitiligo patients and controls were identified using PubMed/Medline and Embase databases. The relationships between the VDR ApaI, TaqI, BsmI, and TaqI polymorphisms and vitiligo were investigated using meta-analyses of all participants and Asian, Arab, European, and Latin American groups.

Results

This meta-analysis included 13 papers with 2034 patients and 2771 controls. In all individuals, there was no link between vitiligo and the VDR ApaI A allele (OR = 0.889, 95% CI = 0.713–1.109, p = 0.298). However, in Asians (OR = 0.721, 95% CI = 0.553–0.940, p = 0.016) but not in Europeans or Arabs, there was a link between the VDR ApaI A allele and vitiligo. Utilizing recessive, dominant, and homozygote contrast models, a link between vitiligo and the VDR ApaI polymorphism was discovered in Asians. Meta-analysis of the VDR BsmI polymorphism showed a significant association between vitiligo and the B allele (OR = 0.812, 95% CI = 0.686–0.961, p = 0.015). In contrast, no connection between vitiligo and VDR polymorphisms was identified for TaqI and FokI polymorphisms.

Conclusion

In the Asian population, ApaI and BsmI polymorphisms in VDR have been correlated to vitiligo susceptibility. However, TaqI and FokI polymorphisms in VDR are not associated with vitiligo susceptibility in European, Asian, Arab, and Latin American populations.  相似文献   

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Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D3 analogue has anti-psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP-based and haplotype-based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over-represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x2 = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.  相似文献   

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Background:  Methylenetetrahydrofolate reductase (MTHFR) is involved in the formation of methyl donors, which contribute to DNA methylation. DNA methylation is an essential epigenetic feature playing a critical role in gene regulation and cellular differentiation. In addition, MTHFR activity affects plasma homocysteine levels. A functional polymorphism in the MTHFR gene (677C>T, rs1801133) leading to reduced enzyme activity has been associated with chronic plaque psoriasis in a Chinese population. This finding, however, has not yet been either confirmed or refuted in other populations. The purpose of the present study was to investigate a hypothesized association between the MTHFR 677C>T polymorphism and the presence of chronic plaque psoriasis in a Caucasian population.
Methods:  Genotypes for the MTHFR 677C>T polymorphism were determined in 310 patients and 247 control subjects. In a subgroup of 33 patients and 33 sex- and age-matched control subjects, fasting plasma homocysteine concentrations were determined by high-performance liquid chromatography and immunological assays were used for the measurement of folate and vitamin B12.
Results:  Prevalence of the homozygous MTHFR 677TT genotype did not significantly differ between patients and controls (15.2% vs 11.7%, P  = 0.24). Mean plasma homocysteine concentrations were significantly higher in psoriasis patients than among control subjects (13.5 ± 5.3 μmol/l vs 11.0 ± 2.2 μmol/l, P  = 0.026). No significant differences between either mean plasma folate or vitamin B12 concentrations were observed between both groups.
Conclusion:  Our data suggest that the MTHFR 677C>T gene polymorphism is not associated with chronic plaque psoriasis among Caucasians.  相似文献   

10.
目的:探讨银屑眉病患者的维生素D受体(VDR)基因多态性与外周血自然杀伤(NK)细胞、T淋巴细胞亚群的关系。方法:采用聚合酶链反应(PCR)、限制性内切酶酶切技术(RFLP),以及流式细胞仪对112例无血缘关系的银屑病患者和108名无血缘关系的健康人VDR基因型进行分析,并对其外周血NK、CD3、CD4、CD8细胞进行测定。结果:银屑病患者与健康人的VDR基因型的分布情况有明显不同,纯合子AA、杂合子Bb基因型在银屑病患者中出现的频率明显高于健康人。银屑病患者CD4、CD8细胞均显著高于健康人,而Bb基因型患者的NK细胞显著高于健康人,CD3细胞明显低于健康人.结论:纯合子AA基因型或杂合子Bh基因型的出现可能增加汉族人患银屑病的危险性。Bb基因型患者可能存在免疫缺陷。  相似文献   

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BackgroundThe vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem-cell proliferation, and microbial defense.ObjectiveTo evaluate the association between the VDR and psoriasis in the northeastern Chinese Han population.MethodsIn this case–control study, 342 patients with psoriasis and 341 controls were genotyped for five common VDR gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) by the Multiplex SNapSHOT method.ResultsThe frequency of ApaI (rs7975232) allele A was significantly increased in psoriasis relative to the control group (27.8% vs. 22.1%, p = 0.018); the allele A of the ApaI polymorphism showed a 1.35-fold increased risk of developing psoriasis. Haplotype analyses showed the BsmI/ApaI/TaqI/Cdx2/FokI GATGC to be significantly over-represented in psoriasis patients compared with controls (p = 0.012). The BsmI/ApaI/TaqI haplotype GCT was presented to a lesser extent in psoriasis patients in comparison with control patients (72.2% vs. 77.9%, p = 0.012).ConclusionsThese data suggest that VDR polymorphisms are associated with psoriasis in Northeastern Han Chinese population.  相似文献   

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Abstract: Vitamin D‐binding protein (VDBP) single nucleotide polymorphisms (SNP) may affect skin carcinogenesis. The objective was to test the association between two functional VDBP SNPs and the susceptibility to (multiple) basal cell carcinomas (BCCs). Of the 7983 participants, 5790 (72.5%) and 5823 (72.9%) participants were genotyped for rs7041 and rs4588, respectively, and three haplotypes (Gc1s, Gc2 and Gc1f) were analysed. Two hundred and thirty‐three persons developed a BCC of whom 122 (52.4%) developed multiple BCCs during a mean follow‐up of 11.6 years. The VDBP genotype was not associated with (multiple) BCC development using Cox proportional hazards and Andersen‐Gill analyses, respectively. Stratifying age groups demonstrated that in the youngest age‐group, the A/T variant of rs7041 was associated with BCC development [adjusted hazard ratio (HR) = 1.88 (95%CI 1.10–3.20)], while homozygote Gc1s carriers had a significantly lower BCC risk [adjusted HR = 0.53 (95%CI 0.31–0.91)]. In conclusion, the VDBP polymorphisms were not associated with susceptibility to (multiple) BCCs, but age–gene interactions were observed.  相似文献   

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Background Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. Objectives To search for novel common polymorphisms in the proximal 5′ regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Methods Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Results Single locus analysis showed no significant association. Haplotype T1686–T3944 appeared to confer a significantly higher risk for BCC development (odds ratio 2·98, 95% confidence interval 2·55–3·48; P = 0·001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5′UTR. Two novel alleles of the ‐4 (CGG)n microsatellite were identified. No association of this microsatellite with BCC was observed. Conclusions Haplotypes containing T1686–T3944 alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5′ regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.  相似文献   

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Background. Vitamin D analogues have been found to be effective in treating the skin lesions of psoriasis. The therapy is thought to work through the vitamin D receptors, resulting in alteration of the proliferation/differentiation balance of the cells. Vitamin D also has an effect on T helper cells, which have a major role in the pathogenesis of psoriasis. There is controversy about the association of vitamin D receptor gene polymorphisms with psoriasis in different populations, and it is a factor that might influence the treatment of these patients. Aim. To study vitamin D receptor gene polymorphisms using two restriction enzymes in a group of Egyptian patients with psoriasis. Methods. In total, 50 patients with psoriasis were examined using restriction fragment length polymorphism analysis to study ApaI and TaqI genotypes of the vitamin D receptor in a sample of Egyptian patients, and compared with 50 healthy control subjects. Results. We did not find any significant difference in ApaI and TaqI vitamin D receptor gene polymorphisms between patients and controls. Conclusions. There is ethnic variability in vitamin D receptor gene polymorphisms. The lack of significant prevalence of the studied gene polymorphisms in our population suggests that their association with other functionally known gene polymorphism might have a role in the pathogenesis of psoriasis.  相似文献   

16.
Background Vitamin D mediates immunomodulatory functions and its deficiency has been associated with an increased prevalence of immunological diseases including systemic lupus erythematosus (SLE). Chronic discoid or subacute cutaneous lupus erythematosus (CLE) are ultraviolet (UV)‐triggered skin diseases. As vitamin D is mostly UV‐derived and not from nutrition, its deficiency is frequent especially during the UV‐deprived winter months. Objective To compare the vitamin D status of patients with CLE with patients with type I allergy and healthy individuals during the summer or winter months. Methods The vitamin D status of patients with CLE (n = 41) was compared with patients with type I allergy (n = 24), healthy individuals (n = 25) and a reference pool (n = 1951) by means of concentrations of circulating storage metabolite 25‐hydroxyvitamin D in the summer and winter. Results Serum 25‐hydroxyvitamin D concentrations were lower during the winter in the reference population, and type I allergic and healthy individuals (29·2–35·5 nmol L?1) compared with the summer months (56·3–89·8 nmol L?1) and paralleled by the prevalence of vitamin D deficiency (serum 25‐hydroxyvitamin D < 50 nmol L?1; winter: 70·8–73·4%, summer: 34·9–39·4%). In contrast, vitamin D deficiency in patients with CLE was prevalent throughout the year (summer: 85·7%, winter: 97·1%). In patients with CLE with concomitant prednisolone treatment, the 25‐hydroxyvitamin D serum levels were comparable with (mean daily intake 877 IU) or without vitamin D supplementation during summer or winter (P = 0·75 and P = 0·14, respectively). Conclusions  Our data identify vitamin D deficiency in patients with CLE throughout the year and indicate that monitoring and correcting the vitamin D status should be considered to prevent bone demineralization and fractures and to modulate beneficially immunological dysfunction.  相似文献   

17.
Sunlight causes DNA damage but also induces production of vitamin D whose metabolite 1,25-(OH)2D3 has antiproliferative and pro-differentiative effects in both melanocytes and cutaneous melanoma (CM) cells mediated through the vitamin D receptor (VDR). We hypothesized that genetic polymorphisms of VDR are associated with risk of CM. In a hospital-based case-control study of 602 non-Hispanic white CM patients and 603 cancer-free control subjects frequency matched by age and sex, we genotyped two VDR polymorphisms (TaqI and FokI) and assessed their association with CM risk. We found that a significantly decreased risk was associated with VDR-TaqI Tt (adjusted odds ratio (OR), 0.70; 95% confidence interval (CI), 0.54-0.90) and Tt+tt (OR=0.70; 95% CI, 0.55-0.89) genotypes, compared with the VDR-TaqI TT genotype, whereas an increased risk was associated with VDR-FokI Ff genotype (OR=1.32; 95% CI, 1.03-1.68), and a borderline significantly increased risk was associated with Ff+ff (OR=1.26; 95% CI, 1.00-1.59) genotypes, compared with the VDR-FokI FF genotype. In conclusion, genetic variants (i.e., TaqI t protective allele and FokI f risk allele) in VDR may alter risk of CM.  相似文献   

18.
目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因第四外显子第677位C→T突变与系统性红斑狼疮(SLE)的相关性。方法 检测40例SLE患者和20例正常人对照组血浆同型半胱氨酸水平,用聚合酶链反应(PCR)-限制性片段长度多态性法作MTHFR基因分型。结果 SLE患者组血浆同型半胱氨酸水平明显高于正常人对照组.而活动期SLE患者与非活动期SLE患者之间血浆同型半胱氨酸水平差异无统计学意义。SLE患者组MTHFR基因TT型占62.5%,明显高于其他两种基因型和正常人对照组(15%)。MTHFR基因677位发生C→T突变可导致血浆同型半胱氨酸水平明显升高,且TT型的效应要明显强于CT型的效应。结论 MTHFR基因多态性是影响SLE患者同型半胱氨酸水平的主要因素之一。MTHFR基因第677位TT型是SLE的易感基因或与易感基因紧密连锁。  相似文献   

19.
We analysed the correlation between the expression of HIF‐1α (hypoxia‐inducible factor 1 alpha), the nuclear receptors: VDR (vitamin D receptor), RORα (retinoic acid receptor‐related orphan receptor alpha), and RORγ and CYP24A1 (cytochrome P450 family 24 subfamily A member 1) and CYP27B1 (cytochrome P450 family 27 subfamily B member 1), enzymes involved in vitamin D metabolism. In primary and metastatic melanomas, VDR negatively correlated with nuclear HIF‐1α expression (= ?.2273, P = .0302; = ?.5081, P = .0011). Furthermore, the highest HIF‐1α expression was observed in pT3‐pT4 VDR‐negative melanomas. A comparative analysis of immunostained HIF‐1α and CYP27B1 and CYP24A1 showed lack of correlation between these parameters both in primary tumors and melanoma metastases. In contrast, RORα expression correlated positively with nuclear HIF‐1α expression in primary and metastatic lesions (r = .2438, P = .0175; r = .3662, P = .0166). Comparable levels of HIF‐1α expression pattern was observed in localized and advanced melanomas. RORγ in primary melanomas correlated also positively with nuclear HIF‐1α expression (r = .2743, P = .0129). HIF‐1α expression was the lowest in localized RORγ‐negative melanomas. In addition, HIF‐1α expression correlated with RORγ‐positive lymphocytes in melanoma metastases. We further found that in metastatic lymph nodes FoxP3 immunostaining correlated positively with HIF‐1α and RORγ expression in melanoma cells (r = .3667; P = .0327; r = .4208, P = .0129). In summary, our study indicates that the expression of VDR, RORα and RORγ in melanomas is related to hypoxia and/or HIF1‐α activity, which also affects FoxP3 expression in metastatic melanoma. Therefore, the hypoxia can affect tumor biology by changing nuclear receptors expression and molecular pathways regulated by nuclear receptors and immune responses.  相似文献   

20.
Reports have highlighted serum vitamin D deficiency and reduced 1,25‐dihydroxyvitamin D(3) receptors(VDR) expression on hair follicles of alopecia areata(AA) patients. Very few studies have demonstrated efficacy of topical calcipotriol (vitamin D analogue) in AA. We intended to study the efficacy of calcipotriol lotion 0.005% in AA and correlate its outcome with serum vitamin D levels. We conducted a prospective study, in which 22 patients with AA were treated with calcipotriol lotion 0.005% twice daily for 3 months. Clinico‐epidemiological parameters including severity of AA and SALT score were calculated at baseline and at 12 weeks. Hair regrowth was assessed monthly at 4, 8, 12 weeks. Serum vitamin D levels were measured at baseline. After 12 weeks of treatment, hair regrowth was observed in 13 (59.1%) patients. Mean period for onset of disease stabilization and hair regrowth was 4 weeks and 4.21± 2.13 weeks, respectively. Among these 13 patients, SALT50 and SALT100 was observed in 6(46.2%) and 2(9%) patients, respectively. Response to treatment was better in patients with lower vitamin D levels (p < .009). Topical calcipotriol can be an alternative treatment in AA and it could prove to be more useful in patients who are vitamin D deficient.  相似文献   

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