Alleles of keratin 1 in families and populations

Keratin 1 is found in the upper layers of the epidermis, on the surface of endothelial cells and in the membrane of the neuroblastoma NMB7. It is important for the structural integrity of the skin, has been found to regulate the activity of kinases, such as protein kinase C (PKC) and SRC, to participate in complement activation by the lectin pathway and to be involved in fibrinolysis, angiogenesis and the response to oxidative stress. Studies of the polymorphisms of the Keratin 1 (KRT1) gene have been driven mostly by interest in its role in skin diseases. However, much of the KRT1 variation occurs in normal populations and is not associated with dermal pathology. In the present experiments, we have investigated the polymorphism of KRT1 genes by nucleotide sequencing in normal families and normal populations of European, African, Hispanic and Asian background. The frequencies of the KRT1 alleles were strikingly different in the four ethnic groups and most of the mutations resulted in amino acid substitutions, with only 3 out of 19 being synonymous. Analysis of selective neutrality by the Ewens–Watterson and Tajima D statistics showed that KRT1 allele homozygosity was decreased in three of the populations suggesting that KRT1 genes may be under the influence of balancing selection. It is possible that the role of KRT1 as a receptor, rather than its structural function in the epidermis, is what drives the selective forces that are apparent in the inheritance of this gene.     

Peak Bone Mineral Density of Physically Active Healthy Indian Men With Adequate Nutrition and No Known Current Constraints to Bone Mineralization

We undertook this study to characterize peak bone density and evaluate its determinants in a healthy cohort of young adult male paramilitary personnel. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 473 healthy men aged 21–40 yr. The effect of anthropometry and biochemical parameters on BMD was determined. Mean BMD values of L1–L4, forearm, total hip, and femoral neck were 1.170 ± 0.137, 0.755 ± 0.089, 1.129 ± 0.130, and 1.115 ± 0.133 g/cm², respectively. BMD values for 31- to 40-yr age group were lower than those of 20- to 30-yr age group except for forearm, which was higher in the former. Significant positive correlation was observed between height, weight, and body mass index with BMD. On multivariate regression analysis, weight was the most consistent contributor to variance in the BMD. Compared with age-matched US males, BMD of total hip and femoral neck were higher for Indian paramilitary personnel by 3.58% and 4.2%, whereas lumbar spine BMD was lower by 4.1%. In conclusion, peak BMD in healthy Indian males was achieved by 30 yr of age at lumbar spine and hip, with weight being the most consistent contributor to variance in BMD. Peak BMD in this population was comparable to that reported in white US males.