Skin is the human body’s largest organ and the first to contact various environments. There are considerable variations of normal skin characteristics within and between populations. For example, skin containing more melanin looks darker, people with reduced axial sweating tend to have less body odor, and skin with higher lipid and water content has an improved barrier. For decades, dermatologists have been developing new methods to measure differences in normal skin characteristics. However, most of these studies were carried out at the clinical level. Research at the molecular level, in contrast, has become more common only in the last decade.
Many characteristics of normal skin have an underlying genetic component. In particular, skin characteristics that differ substantially between ethnic groups are predicted to have a basis in genetics. The use of genomic technologies to understand skin variation has the potential to spur major breakthroughs in this field. When affordable genomic technologies were introduced several years ago, it vastly improved our understanding of the genetic determinants regulating pigmentation (
Sturm, 2009
). However, skin pigmentation has thus far been the only well-studied characteristic of normal skin, perhaps because it is a conspicuous trait and varies significantly between and within populations. This trait also has high heritability, ranging from 0.5 to 0.8 in reported studies (Barsh, 2003
), and can be quantified relatively easily by reflectance spectrophotometry. These factors make skin pigmentation an ideal trait to study in a genome-wide scan framework. Here, we list a number of understudied normal skin characteristics that have significant ethnic differences, high heritability, and functional implications.Eccrine sweat glands and thermoregulation
Human sweat glands are generally divided into two types: eccrine glands and aprocrine glands. Eccrine glands are distributed all over the body and produce sweat consisting primarily of water and sodium chloride. Eccrine glands are responsible for thermoregulation, as the skin temperature is cooled down by the evaporation of the water in sweat. The amount of sweat evaporated has typically been measured by a ventilated capsule method (
Fan, 1987
). The total number of eccrine glands can be measured by noninvasive in vivo confocal microscopy scan (Nehal et al., 2008
). Early studies have shown considerable heritability (0.66) in the number of sweat pores (Scobbie and Sofaer, 1987
) among different individuals. Activated eccrine glands have been measured by chemical methods based on the starch/iodine reaction (Muller and Kierland, 1959
). Kawahata and Sakamoto, 1951
reported ethnic differences in activated sweat glands. They showed that tropical populations have significantly more activated sweat glands. Furthermore, the number of activated eccrine glands is associated with the V370A variant of the EDAR gene in both human and mouse (Kamberov et al., 2013
). This V370A variant manifests different allelic frequencies in ethnic groups; it is present at a high frequency in East Asians and nearly absent in Europeans and Africans.Apocrine sweat glands and body odor
Apocrine sweat glands are distributed primarily in the axillary and genital areas, and are not active until puberty. The secretion of apocrine glands contains proteins and fatty acids. While the secretion itself is odorless, it contains a variety of odor precursors that are transformed into volatile odoriferous molecules by bacterial enzymes on the skin surface. It is well recognized that Caucasians and Africans possess a strong axillary odor, whereas many East Asians have only a faint acidic odor. It is interesting that East Asians are reported to have significantly smaller number of apocrine glands than Caucasians (
Bang et al., 1996
).The known major axillary odorants, the related precursors, and the enzymes involved have been measured and described in detail in
Martin et al., 2010
. The presence of these substances in axillary sweat can be reliably quantified by liquid chromatography mass spectrometry. A number of the substances have been reported to be associated with a variant of the ABCC11 locus (Martin et al., 2010
, Zeng et al., 1992
). It has been demonstrated that one of the major axillary odorants, 3-methyl-2-hexenoicacid, is carried to the skin surface bound to apoD. It has been reported that while Chinese individuals have only diminished or nondetectable levels of apoD in axillary skin extracts, Europeans and Africans have easily detectable levels of apoD (Jacoby et al., 2004
).Sebaceous glands and skin oiliness
Sebaceous glands are found all over the human body except on the palms and soles, and have a great concentration on the face and scalp. The number of sebaceous glands remains approximately constant throughout life, whereas their size tends to increase with age. The most obvious function of the sebaceous gland is to excrete sebum, which contains different types of lipids and makes the skin “oily,” There are considerable ethnic differences in several phenotypes related to sebaceous glands. Africans reportedly have significantly larger sebaceous gland size than other groups, while East Asians have the smallest pore size (
Kligman and Shelley, 1958
). A twin study showed significant heritability in both saturated and monounsaturated iso-even fatty acids of the sebum (0.497 and 0.385, respectively) (Stewart et al., 1986
).Stratum corneum structure and barrier function
The stratum corneum is the outermost layer of the epidermis. The purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals, and mechanical stress. The protection required in various environments during human evolution might be different, which in turn led to substantial differences observed in different ethnic groups. For example,
Kompaore et al., 1993
reported higher transepidermal water loss in Africans and East Asians than in Caucasians. Caucasians also have the lowest water content level (Hillebrand et al., 2001
). Although the thickness of stratum corneum is similar between Africans and Caucasians, Africans have significantly smaller corneocyte cell size and more layers. There have also been studies on lipid content of stratum corneum, suggesting Africans have higher lipid content than Caucasians (Reinertson and Wheatley, 1959
, Weigand et al., 1974
).We expect, in the coming years, genome-wide scans to identify causal variants associated with normal skin characteristics. The breakthroughs will bring crucial insights in the genetics and biological mechanisms of the normal skin characteristics.
Conflict of Interest
The authors state no conflict of interest.
Acknowledgments
Publication of this supplement is supported by the Chinese Medical Association and Hampton Sevson Ltd.
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