Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6.

A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OR(Overall) = 1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR = 1.27 (1.16-1.34)) and Mongolian (OR = 2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis.

Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians.

We performed a genome-wide association study with 23,465 microsatellite markers to identify genes related to adult height. Selective genotyping was applied to extremely tall and extremely short individuals from the Khalkh-Mongolian population. Two loci, 8q21.13 and 15q22.33, which showed the strongest association with microsatellites were subjected to further analyses of SNPs in 782 tall and 773 short individuals. The most significant association was observed with SNP rs2220456 at 8q21.13 (P = 0.000016). In the LD block at 15q22.32, SNP rs8038652 located in intron 1 of IQCH was strongly associated (P = 0.0003), especially the AA genotype of the SNP under a recessive model was strongly associated with adult height (P = 0.000046).

Alu insertion polymorphisms in Native Americans and related Asian populations.

BACKGROUND: Alu insertions provide useful markers for the study of inter-population affinities and historical processes, but data on these systems are not numerous in Native Americans and related populations. AIM: The study aimed to answer the following questions: (a) do the population relationships found agree with ethnic, historical and geographical data? and (b) what can heterozygote levels and associated results inform us about the events that led to the colonization of the New World? SUBJECTS AND METHODS: Twelve Alu insertion polymorphisms were studied in 330 individuals belonging to South American Native, Siberian and Mongolian populations. These data were integrated with those from 526 persons, to ascertain the relationships between Asian, Northern Arctic and Amerindian populations. RESULTS: A decreasing trend concerning heterozygosities and amount of gene flow was observed in the three sets, in the order indicated above. Most results indicated the validity of these subdivisions. However, no clear structure could be observed within South American Natives, indicating the importance of dispersive (genetic drift, founder effects) factors in their differentiation. CONCLUSIONS: The answers to the questions are: (a) yes; and (b) an initial moderate bottleneck, intensified by more recent historical events (isolation and inbreeding), can explain the current Amerindian pattern of diversity.

Genetic features of Khoton Mongolians revealed by SNP analysis of the X chromosome.

The Khoton Mongolian population is a small and relatively isolated ethnic group residing predominantly in the northwestern part of Mongolia. A recent genetic study of the Y chromosome revealed that the major Mongolian ethnic groups have a relatively close genetic affinity to populations in the northern part of East Asia, while the Khoton population reflected an apparent genetic differentiation from the other Mongolian populations. To further investigate the genetic features of the Khoton and the other Mongolian populations, we analyzed the single nucleotide polymorphisms (SNPs) in the Xq13.3 region, which is thought to have an extremely low level of recombination in the human X chromosome. We found that the frequency distribution of Xq13.3 haplotypes in the Khoton population was substantially different from those in three other Mongolian populations (Khalkh, Uriankhai, and Zakhchin). The same relationship was also revealed by the results from the population tree and principal-component (PC) analysis based on the allele frequencies. These results are largely consistent with the hypothesis that the Khoton population descended from a nomadic tribe of Turkish origin, which has been supported by previous anthropological, historical, and Y-chromosome studies. However, the population structure analysis produced an additional finding, namely, that the Khoton population is likely to be an admixed population.

Genetic features of Mongolian ethnic groups revealed by Y-chromosomal analysis.

About 20 ethnic groups reside in Mongolia. On the basis of genetic and anthropological studies, it is believed that Mongolians have played a pivotal role in the peopling of Central and East Asia. However, the genetic relationships among these ethnic groups have remained obscure, as have their detailed relationships with adjacent populations. We analyzed 16 binary and 17 STR polymorphisms of human Y chromosome in 669 individuals from nine populations, including four indigenous ethnic groups in Mongolia (Khalkh, Uriankhai, Zakhchin, and Khoton). Among these four Mongolian populations, the Khalkh, Uriankhai, and Zakhchin populations showed relatively close genetic affinities to each other and to Siberian populations, while the Khoton population showed a closer relationship to Central Asian populations than to even the other Mongolian populations. These findings suggest that the major Mongolian ethnic groups have a close genetic affinity to populations in northern East Asia, although the genetic link between Mongolia and Central Asia is not negligible.

Aspirin induces hepatoma-derived cell apoptosis via a hydrogen peroxide-dependent pathway.

Here we studied whether aspirin (ASA) has any influence on viability of human hepatoma-derived SKHep-1 cells and whether hydrogen peroxide (H(2)O(2)) has any relation with this effect. ASA inhibited SKHep-1 cell proliferation dose- and time-dependently. Intracellular H(2)O(2) increased as early as 15 min after ASA supplementation. Cellular apoptosis correlated with an increase in intracellular H(2)O(2) level. Moreover, in the presence of a catalase inhibitor-aminotriazol, ASA showed more apoptotic effect on SKHep-1 cells with increasing intracellular H(2)O(2) level. In conclusion, the present results shows that ASA induced SKHep-1 cell apoptosis has a relation with an early increase in intracellular H(2)O(2) level and catalase inhibitor synergizes to induce this process.

Umbilical cord blood dendritic cells are a rich source of soluble HLA-DR: synergistic effect of exosomes and dendritic cells on autologous or allogeneic T-Cell proliferation.

In this study, we compared soluble HLA-DR (sHLA-DR) production in the culture supernatants of various cell sources [T and B cells, monocytes and dendritic cells (DCs) either from adult peripheral blood (PB) or umbilical cord blood (UCB)]. DCs produced the highest amount of sHLA-DR molecules as compared to other cell sources, with UCB DCs producing the highest amount. Different kinetics of sHLA-DR production were found between immature and mature UCB DCs (mDC, iDC) (derived either from CD34(+) or CD14(+) cells). Maximum production of sHLA-DR was observed in 72-hour culture supernatants of both CD34- and CD14-derived mDCs, whereas it peaked in the 24-hour culture supernatants from iDC. sHLA-DR molecules were pelleted after sequential centrifugation from UCB CD34(+) DCs and were found to contain both 36 kD alpha-chain and 29 kD beta-chain of HLA-DR, CD86, and Fas molecules. These sHLA-DR containing vesicles/exosomes alone evoked weak proliferative responses from autologous and allogeneic T cells, but the immune response was significantly increased when vesicles/exosomes were presented with DCs.

Human umbilical cord blood NK T cells kill tumors by multiple cytotoxic mechanisms.

Natural killer (NK) T cells are restricted by CD1d and play an important role in the rejection of malignant tumors, but how kill these tumors is unclear. To investigate this, we cultured Valpha24+CD4+ NK T cells in human umbilical cord blood, which was enriched by immunomagnetic beads. In short-term (4 h) cytotoxicity assays, the NK T cells could kill only those targets expressing CD1d. In longer cytotoxicity assays (20 h), however, the NK T cells were able to kill all the tumors, regardless of CD1d expression. When each of the perforin, Fas-FasL, and TNF-alpha cytotoxic mechanisms were blocked, it was apparent that perforin killing dominated in both the short- and long-term assays. In the short-term assay, perforin killing required that the targets expressed CD1d, but killing was more efficient if Fas was present because then the Fas-FasL mechanism was also used. Thus, cells that lacked Fas and CD1d and were not killed in the 4-h assay, were instead lysed in 20-h assay through a combination of perforin and TNF-alpha killing. NK T cells can kill tumor targets by perforin, Fas-FasL, and TNF-alpha mechanisms. TNF-alpha killing requires longer contact between effectors and targets, suggesting that TNF-alpha acts by enhancing perforin killing.