Investigation of the cause of Alopecia with specific emphasis on Comparison of the Effect of SOX21 Gene Relates and Deficiency of Minerals and Vitamins in Diets
Alopecia is a medical condition that results in the loss of hair on the body (Price, Willey, & Chen, 2005; Al-Khenaizan, & Vitale, 2003). The term alopecia is generally used in reference to pattern or androgenic alopecia (AGA). There is adequate support for the assertion that certain mineral deficiencies, for instance iron deficiency, may result in the loss of bodily hair and therefore alopecia (Vanderford, Greer, Sharp, Chichlowski, Clayburn, Angelica, & Hale, 2010; Kruse, & Feldmann, 1995; White, Currie, & Williams, 1994).
Overall, alopecia is a complex polygenic condition that is likely to be a result of the interaction between environmental and genetic factors that trigger immune dysfunction (Gilhar, 2010; Esfandiarpour, Farajzadeh, & Abbaszadeh, 2008). Lack of certain minerals in the body is known to cause deficiencies and therefore dysfunction of the immune system (Orban et al, 2007; Xie et al, 2002; Boffa, Wood, & Griffiths, 1995; Zandman-Goddard, & Shoenfeld, 2007).
Current studies have explored the role played by either minerals or the SOX21 gene in the development and progression of alopecia (Al-Herz, & Nanda, 2011). No study has so far sought to compare the role played by mineral deficiency and the SOX 21 gene in the development of alopecia with the aim of determining the most influential factor. Findings from such a study will help shed light on which, factor should be the focus when developing corrective measures.
In addition, the studies are limited to unique manifestations of alopecia such as alopecia areata (AA) and AGA (Lenane, Pope, & Krafchik, 2005). The problem is that there are two competing viewpoints on the cause of alopecia: the SOX21 gene and mineral deficiency. It is not however clear which of the two factors is responsible for most cases of alopecia. The aim of the proposed study is thus to compare the influence of the SOX21 gene and minerals (vitamins and minerals) in the development and progression of alopecia.
Selenium is a critical component in the antioxidant defence system. Studies reveal that the therapeutic window of selenium is narrow (Cobb, Wong, Yip, Martinick, Bosnich, Sinclair, Craig, Saffery, Harrap, & Ellis, 2011). When the levels of selenium are over 11g/g, toxicity occurs, whereas when the levels are lower than 0.11g/g, deficiency is witnessed (Cobb, Wong, Yip, Martinick, Bosnich, Sinclair, Craig, Saffery, Harrap, & Ellis, 2011). Previous studies revealed that excess or deficiency of Selenium results in abnormalities such as change in the texture of hair, hypopigmentation, and even alopecia (Nalls et al, 2011; Gönül et al, 2009; Sengupta et al, 2010).
The growth of hair is maintained through a cyclic process that includes the periodic regeneration of hair follicles (Shrivastava, 2009; Akar, Arca, Erbil, Akay, & Sayal, 2002). There is little known from empirical and clinical evidence on the cellular and molecular mechanism responsible for the regulation of the layered differentiation of hair follicles (Shrivastava, 2009). Studies on mice however reveal that the cyclic alopecia phenotype can result from disruptive targeting of specific gene expression (Miwa, & Kondo, 2003; Cunningham, Giuffrida, & Roberts, 2009). The SOX21 gene is responsible for the encoding of the HMG-box protein. Thus, when the SOX21 gene is disrupted, progressive hair loss occurs (Shrivastava, 2009). The disruption of the SOX21 gene results in progressive hair loss after morphogenesis of the first hair follicle (Carroll, McElwee, Byrne, & Sundberg, 2002).
SOX21 is expressed in the progenitor cells and the cuticle layer of hair shafts in both humans and mouse (Deng, Huang, Zhou, Wang, You, Song et al, 2006). Lack of this gene results in loss of interlock structures required for hair shafts to be anchored in the hair follicles (Benson et al, 2006; Klein et al, 2005). In a mouse, the expression of genes that encode keratins and keratin binding proteins in hair shaft cuticles is down-regulated in the mice that lack the SOX21 gene (Oertelt, Selmi, Invernizzi, Podda, & Gershwin, 2005). The implication of these findings is that SOX21 is a master regulator of hair shaft cuticle differentiation.
Studies reveal that the etiological factors for AGA are genetic predisposition and androgen dependency (Cobb, Zaloumis, Scurrah, Harrap, & Ellis, 2010; Ellis, Sinclair, & Harrap, 2002). Whereas hair loss is often considered a cosmetic rather than a medical condition, new evidence reveals that the mechanism influencing the aetiology of AGA may aggravate underlying medical conditions (Cobb, Zaloumis, Scurrah, Harrap, & Ellis, 2010).
The lymphocytic infiltration of the dermal papilla and anagen hair bulb is often followed by the aberrant expression of the human leukocyte antigen class I and II and the intercellular adhesion molecule 1 on the follicular epithelium (Cobb, Wong, Yip, Martinick, Bosnich, Sinclair, Craig, Saffery, Harrap, & Ellis, 2011). This observation highlights the important role played by immune dysfunction in the pathogenesis of Alopecia Areata (AA). A widely accepted hypothesis is that AA is a t-cell mediated autoimmune responses that targets unknown antigens in the anagen-phase of the hair follicles (Ito, Ito, Saatoff, Hashizume, Fukamizu, Nickoloff et al, 2008; Richards et al., 2008; Hillmer et al, 2008). Other postulations (Esfandiarpour, Farajzadeh, & Abbaszadeh, 2008) assert that the compromise of the immune privileges (the ability to tolerate antigens without elicitation of inflammatory responses) in normal hair follicles, resulting in part through the mediation of the interferon gamma, plays a role in the pathogenesis and susceptibility of AA.
Recent identification of susceptibility loci including positive family history and twin concordance rates point to the likelihood that genetics play an important role in the aetiology of Alopecia (Coda, Qafalijaj, Seiffert-Sinha, & Sinha, 2010; Bergman et al, 2005). Epidemiological studies on the other hand reveal that there is a high prevalence of autoimmune diseases such as thyroid disease, vitiligo, and collagen vascular disease in AA patients and their affected or unaffected relatives (Keene, & Goren, 2011; Malloy et al, 1997
From the literature, it is evident that there are two competing views on the causative factors for alopecia. The competing views exist because researchers either analyse alopecia as a problem caused by genes or mineral deficiency, but not both. Whereas one group asserts that the condition is caused by mineral and vitamin deficiency (Cobb et al, 2011; Orban et al, 2007; Xie et al, 2002), others suggest a genetic predisposition (Keene, & Goren, 2011).
After power analysis at 5% significance level and considering the estimates of the number of people affected by alopecia in the UK, the minimum sample size was determined to be 93. About 100 alopecia patients and 100 non-alopecia elderly persons will be recruited from skin experts in the UK for the study during the three-year period. The diagnosis for alopecia will be done using the ICD-10 diagnostic criteria (Cobb et al, 2011). Participants will be required to fast for a period of 12 hours prior to the collection of blood samples.
DNA will be extracted using a phenol chloroform and isoamyl alcohol extraction method. RNA isolation will be done using TRIzol reagent. PCR Amplification, RFLP, and non- denaturing polyacrylamide gel electrophoresis will then be used to determine the levels of expression of the SOX21 gene (Carroll, McElwee, Byrne, & Sundberg, 2002). Blood samples from the participants will be tested for serum iron, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation and serum ferritin levels (Boffa, Wood, & Griffiths, 1995).
A trace mineral test will be used to test the levels of selenium in the plasma. Quantitative Inductively Coupled Plasma-Mass Spectrometry will be used to determine the levels of Selenium in the participants’ urine. The results in both the iron and selenium tests will be calculated and compared with the standard curve (expected levels). Statistical quantitative techniques will then be used to determine any differences.