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Downregulation of KLK4 Gene Detected in East Asians; May Contribute to Specific Dental Traits and Eczema Resistance Found in Asians

Dr. Susana Seixas of the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal, and colleagues have found key differences in a suite of genes important for skin and bone development that may have bestowed specific advantages amongst Asians. The new research was published online on September 29, 2015 in Molecular Biology and Evolution. The article is titled “Adaptive Evolution Favoring KLK4 Downregulation in East-Asians.” The researchers focused on the human kallikrein cluster (KLK), a suite of fifteen genes clustered on the long arm of chromosome 19 that play a key role in human adaptation and reproductive biology. The genes function as molecular scissors called serine proteases, which target and clip other proteins involved in semen function, teeth development, skin and blood pressure maintenance, and even cancer. The team undertook a large study to identify 1,419 DNA differences in the KLK genomic cluster amongst Eastern Asian (Han Chinese and Japanese), African, and European populations by using new DNA data from the recently completed 1000 Genomes project. The most striking differences were narrowed down to two regions near the KLK4 gene, which were found to severely hamper the activity of KLK4 only in Asian populations. This KLK4 downregulation may contribute to dental traits typically found in Asians and be important in controlling skin conditions like eczema, which is much more prevalent in northern Europe than in Asia. "We further predict many effects related to male biology and other physiological functions with possible outcomes in human complex diseases, said Dr. Seixas. "KLK4 is a pervasive protease, expressed in a wide range of tissues, and frequently over-expressed in prostate, ovarian, and breast cancers, where it is thought to play a role in tumor progression and metastasis. We are only at the tip of the iceberg, but one very exciting possibility is that the same differences may confer a selective advantage to offering a reduced risk to several cancer types with lower incidences in East-Asia." The image indicates the 3D structure of the KLK4 protein.

[Press release] [Molecular Biology and Evolution abstract]