TCF7L2 gene polymorphisms and susceptibility to breast cancer: a meta-analysis.

Numerous studies have evaluated the association between TCF7L2 gene polymorphisms (rs12255372 and rs7903146) and breast cancer risk. However, the results have been inconsistent. Therefore, in the current study, we performed a meta-analysis. A systematically literature search of the PubMed and EMBASE databases was conducted in November 2013, and the reference lists of articles were retrieved. A summary odds ratio (OR) with its 95% confidence interval (CI) were calculated to evaluate the strength of association. Publication bias was investigated using Begg's funnel plot. Meta-analysis was performed using STATA package version 12.0. A total of 4 case-control studies met our inclusion criteria, including 4600 cases and 5289 controls. Overall, TCF7L2 gene polymorphisms were significantly associated with an increased risk of breast cancer in genetic comparison models (rs12255372 for GG vs GT: OR = 0.90, 95%CI = 0.83-0.98; rs7903146 for CC vs TT: OR = 0.75, 95%CI = 0.63-0.90, CC vs CT: OR = 0.88, 95%CI = 0.81-0.97, dominant model: OR = 1.16, 95%CI = 1.06-1.27, recessive model: OR = 0.79, 95%CI = 0.67-0.94). This meta-analysis demonstrated that TCF7L2 gene polymorphisms (rs12255372 and rs7903146) are associated with an increased susceptibility to breast cancer. However, further studies including large sample sizes are needed to validate this association.

Uneven evolutionary rate of the melatonin-related receptor gene (GPR50) in primates.

The melatonin-related receptor GPR50 plays an important role in mammalian adaptive thermogenesis in response to calorie intake. The evolutionary history of the GPR50 gene is poorly understood in primates; however, it has been reported that GPR50 is the mammalian ortholog of Mel1c, which has been well characterized. In this study, the complete coding sequences of the GPR50 gene in the Sichuan snub-nosed monkeys (Rhinopithecus roxellana) and Tibetan macaques (Macaca thibetana) were sequenced, and the orthologous nucleotide acid sequences of the GPR50 gene in 11 other primate species were downloaded from GenBank. Thirteen species representing 6 major primate lineages (human, great ape, lesser ape, Old World monkey, New World monkey, and prosimian monkey) were subjected to statistical analyses. A selective test showed that the entire GPR50 gene sequence is under strong purifying selection in these primates but has a significantly different evolutionary rate among the 6 major primate lineages. Notably, both the Homo and Pan branches exhibited an ω ratio >1, indicating accelerated evolution of the two lineages. Further analysis of different domains revealed that the acceleration trend was more significant in the C-terminal domain (CTD). Interestingly, in the alignment of 13 primate GPR50 nucleotide acid sequences, numerous insertions or deletions were only found in the CTD region, implying that this region may play a key role in the process of primate GPR50 evolution. The results provide deeper insight into the functional evolution of GPR50 in mammals at the molecular level.

Plasma nitric oxide levels in newborn infants with sepsis.

Nitric oxide is thought to play an important role in the mediation of the cardiovascular features of septic shock. We determined plasma levels of nitrite and nitrate (not differentiated in measurement) in neonates with sepsis and found these levels to be elevated at the time of entry compared with those of control subjects (p < 0.05); the levels were significantly higher in the patients with sepsis and shock than in those without shock (p < 0.05). Elevations of nitrite plus nitrate were correlated with tumor necrosis factor and severity of illness judged by pediatric risk of mortality (PRISM) scores at onset (p < 0.05). Of 8 newborn infants with a nitrite-plus-nitrate value > 200 mumol/L, 6 had septic shock; none of 12 not reaching that cutoff value had septic shock (p < 0.05). Levels of nitrite plus nitrate were elevated as much in gram-positive as in gram-negative sepsis. We conclude that the determination of circulating plasma levels of nitrite plus nitrate may be useful in forecasting the severity of illness and the occurrence of septic shock; therapeutic approaches associated with inhibition of nitric oxide synthesis may be worth trying in infants with septic shock.