Role of blood-borne factors in sympathoexcitation-mediated hypertension: Potential neurally mediated hypertension in preeclampsia.

Hypertension remains a threat for society due to its unknown causes, preventing proper management, for the growing number of patients, for its state as a high-risk factor for stroke, cardiac and renal complication and as cause of disability. Data from clinical and animal researches have suggested the important role of many soluble factors in the pathophysiology of hypertension through their neuro-stimulating effects. Central targets of these factors are of molecular, cellular and structural nature. Preeclampsia (PE) is characterized by high level of soluble factors with strong pro-hypertensive activity and includes immune factors such as proinflammatory cytokines (PICs). The potential neural effect of those factors in PE is still poorly understood. Shedding light into the potential central effect of the soluble factors in PE may advance our current comprehension of the pathophysiology of hypertension in PE, which will contribute to better management of the disease. In this paper, we summarized existing data in respect of hypothesis of this review, that is, the existence of the neural component in the pathophysiology of the hypertension in PE. Future studies would address this hypothesis to broaden our understanding of the pathophysiology of hypertension in PE.

Identification of differentially expressed genes associated with lung adenocarcinoma via bioinformatics analysis.

Lung adenocarcinoma (LUAD) with extremely high morbidity as well as mortality is still in the exploration stage of pathogenesis and treatment. This study aimed to screen and identify differentially expressed genes (DEGs) associated with LUAD via bioinformatics analysis. Three LUAD microarray datasets, GSE116959, GSE68571 and GSE40791, were selected from the Gene Expression Omnibus (GEO) database to analyze the DEGs. 128 DEGs were identified in all, incorporating 36 upregulated and 92 downregulated. Function and pathway enrichment analyses showed that metabolic pathways were their main signaling pathways. After that, seven hub genes including VWF, SPP1, PECAM1, TOP2A, CDK1, UBE2C and KIF23 were mined by the protein-protein interaction (PPI) network. Gene expression analysis, TNM and survival analysis of these hub genes were performed via Gene Expression Profiling Interactive Analysis (GEPIA) online database. Further analysis indicated that TOP2A, CDK1, UBE2C and KIF23 were related to the stage of LUAD patients and overall survival. Then, we verified the relative expression levels of TOP2A, CDK1, UBE2C and KIF23 in LUAD cell lines by qRT-PCR. In conclusion, this study indicated that the four hub genes screened out by bioinformatics analysis were differentially expressed in LUAD compared to normal sample and might be prognostic markers of LUAD.

Paternal heritage of the Han Chinese in Henan province (Central China): high diversity and evidence of in situ Neolithic expansions.

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China.Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese.Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation.Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the "Major lineages" contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of "Minor lineages" that diverged in the Palaeolithic Age.Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations.

Cebú, Thailand and Taiwanese aboriginal populations according to Y-STR loci.

Here we report for the first time the Y27-STR Yfiler plus profiles of the insular population of Cebú in the central region of the Philippine Archipelago and the general continental population of Thailand, two strategic locations of interest in connection with the Austronesian expansion. Traditionally, the peopling of Taiwan has been envisioned as a single wave of agriculturists migrating from mainland Southeast Asia. Yet, more recent data support a scenario in which a number of migrations from the continent populated the island. Genetic affinity parameters from this study indicate that certain Formosan tribes are genetically closer to geographical distant populations in the Solomon Island than to other nearby Taiwanese tribes. Furthermore, Taiwanese aboriginal populations in this study partition into three clusters, one associated with populations from the Philippines and Thailand, a second one segregating with populations of the Solomon Islands and a third grouping made up exclusively of Taiwanese aboriginal tribes. The populations within each of these three clusters exhibit different degrees of differentiation among them suggesting unique population histories. All together, these differential genetic affinities of specific Taiwanese tribes to groups from different geographical regions and to each other are compatible with multiple origins of the Austronesian expansion from Formosa as well as from mainland Southeast Asia.

[Study of genetic polymorphisms of 7 Y chromosome single nucleotide polymorphism loci among Mongolians from Inner Mongolia Region].

OBJECTIVE: To study the genetic polymorphisms of 7 Y chromosome single nucleotide polymorphisms (Y-SNPs) among unrelated Mongolian males from Inner Mongolia Region. METHODS: Seven Y-SNPs with expected allelic frequencies close to 0.50:0.50 in Mongolian population were selected from databases including HapMap and relevant literature. The Y-SNPs were then analyzed among 95 unrelated male Mongolian DNA samples with ligase detection reaction (LDR) technique. Statistical analysis was carried out with Arlequin 3.5. RESULTS: All of the 7 Y-SNPs had 2 alleles. Seven haplotypes were identified among the 95 samples, with the haplotype diversity (HD) being 0.7990. Except for rs17316007, whose allelic frequencies was 0.832:0.168, each of the remaining Y-SNPs had a allelic frequency close to 0.50:0.50. The gene diversity (GD) for rs17316007 was 0.2825, while those of the remaining Y-SNPs were all greater than 0.4375. CONCLUSION: Except for rs17316007, the other 6 Y-SNPs showed good diversity and genetic polymorphism, and may be used for individual identification and paternity testing for the Inner Mongolia region.

Genome-wide screen for universal individual identification SNPs based on the HapMap and 1000 Genomes databases.

Differences among SNP panels for individual identification in SNP-selecting and populations led to few common SNPs, compromising their universal applicability. To screen all universal SNPs, we performed a genome-wide SNP mining in multiple populations based on HapMap and 1000Genomes databases. SNPs with high minor allele frequencies (MAF) in 37 populations were selected. With MAF from ≥0.35 to ≥0.43, the number of selected SNPs decreased from 2769 to 0. A total of 117 SNPs with MAF ≥0.39 have no linkage disequilibrium with each other in every population. For 116 of the 117 SNPs, cumulative match probability (CMP) ranged from 2.01 × 10-48 to 1.93 × 10-50 and cumulative exclusion probability (CEP) ranged from 0.9999999996653 to 0.9999999999945. In 134 tested Han samples, 110 of the 117 SNPs remained within high MAF and conformed to Hardy-Weinberg equilibrium, with CMP = 4.70 × 10-47 and CEP = 0.999999999862. By analyzing the same number of autosomal SNPs as in the HID-Ion AmpliSeq Identity Panel, i.e. 90 randomized out of the 110 SNPs, our panel yielded preferable CMP and CEP. Taken together, the 110-SNPs panel is advantageous for forensic test, and this study provided plenty of highly informative SNPs for compiling final universal panels.

The Potential Protective Effect of Curcumin on Amyloid-ß-42 Induced Cytotoxicity in HT-22 Cells.

BACKGROUND: We aimed to investigate the effect and mechanism of curcumin (CUR) in Alzheimer's disease (AD). METHODS: Mouse hippocampal neuronal cell line HT-22 was treated with Aß1-42 and/or CUR, and then cell viability was evaluated by cell counting kit 8, Beclin-l level was detected using western blotting, and the formation of autophagosomes was observed by transmission electron microscopy (TEM). Furthermore, transcriptome sequencing and analysis were performed in cells with Aß1-42 alone or Aß1-42 + CUR. RESULTS: Aß1-42 treatment significantly inhibited cell viability compared with untreated cells (P < 0.01). After treatment for 48 h, CUR remarkably promoted cell viability compared with cell treated with Aß1-42 alone (P < 0.01). Compared with cells treated with Aß1-42 alone, the expression of Beclin-1 was slightly reduced in cells with combined treatment of Aß1-42 with CUR (P < 0.05). Consistently, TEM results showed that CUR inhibited the formation of autophagosomes in cells treated with Aß1-42. Furthermore, the protein-protein interaction network showed five key genes, including MYC, Cdh1, Acaca, Egr1, and CCnd1, likely involved in CUR effects. CONCLUSIONS: CUR might have a potential neuroprotective effect by promoting cell viability in AD, which might be associated with cell autophagy. Furthermore, MYC, Cdh1, and Acaca might be involved in the progression of AD.

TRPML1 Participates in the Progression of Alzheimer's Disease by Regulating the PPARγ/AMPK/Mtor Signalling Pathway.

BACKGROUND: TRPML1 is reported to be involved in the pathogenesis of Alzheimer's disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. METHODS: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis. Primary neurons were isolated and treated with the vehicle, Aß1-42 or Aß1-42 + mTOR activator, as well as infected with the recombinant adenovirus TRPML1 overexpression vector in vitro. Cell viability was measured by the MTS assay, and lysosomal Ca2+ was also measured. RESULTS: In the APP/PS1 transgenic mice, TRPML1 was downregulated, the PPARγ/AMPK signalling pathway was activated, the mTOR/S6K signalling pathway was suppressed, and autophagic lysosome reformation (ALR)-related proteins were upregulated. TRPML1 overexpression or treatment with PPARγ and AMPK inhibitors or an mTOR activator reduced the expression levels of ALR-related proteins, rescued the memory and recognition impairments and attenuated neuronal apoptosis in mice with the APP/PS1 transgenes. In vitro experiments showed that TRPML1 overexpression or treatment with the mTOR activator propranolol attenuated the Aß1-42-suppressed cell viability and the Aß1-42-decreased lysosomal [Ca2+] ion concentration in primary neurons. TRPML1 overexpression or treatment with the mTOR activator propranolol also attenuated the Aß1-42-inhibited mTOR/S6K signalling pathway and the Aß1-42-induced ALR-related protein expression levels. CONCLUSION: TRPML1 is involved in the pathogenesis of AD by regulating autophagy at least in part through the PPARγ/AMPK/mTOR signallingpathway.

Curcumin Exerts Effects on the Pathophysiology of Alzheimer's Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression.

BACKGROUND: To validate our speculation that curcumin may ameliorate Alzheimer's disease (AD) pathogenesis by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 (TRPML1) expression levels. METHODS: We developed an animal model presenting AD by APP/PS1 transgenes. The mouse clonal hippocampal neuronal cell line HT-22 was treated with amyloid-ß1-42 (Aß1-42). Curcumin was administrated both in vivo and in vitro. MTS assay was used to detect cell viability, and the lysosomal [Ca2+] ion concentration was detected. The number of autophagosomes was detected by the transmission electron microscopic examination. Illumina RNA-seq was used to analyze the different expression patterns between Aß1-42-treated cells without and with curcumin treatment. The protein level was analyzed by the Western blotting analysis. PI(3,5)P2 or TRPML1 was knocked down in HT-22 cells or in APP/PS1 transgenic mice. Morris water maze and recognition task were performed to trace the cognitive ability. RESULTS: Curcumin increased cell viability, decreased the number of autophagosomes, and increased lysosomal Ca2+ levels in Aß1-42-treated HT-22 cells. Sequencing analysis identified TRPLML1 as the most significantly upregulated gene after curcumin treatment. Western blotting results also showed that TRPML1 was upregulated and mTOR/S6K signaling pathway was activated and markers of the autophagy-lysosomal system were downregulated after curcumin use in Aß1-42-treated HT-22 cells. Knockdown of PI (3,5)P2 or TRPML1 increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in Aß1-42-treated HT-22 cells, inhibited mTOR/S6K signaling pathway, increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in APP/PS1 mice. Besides, knockdown of PI(3,5)P2 or TRPML1 reversed the protective role of curcumin on memory and recognition impairments in mice with APP/PS1 transgenes. CONCLUSION: To some extent, it suggested that the effects of curcumin on AD pathogenesis were, at least partially, associated with PI(3,5)P2 and TRPML1 expression levels.

Revisiting the male genetic landscape of China: a multi-center study of almost 38,000 Y-STR haplotypes.

China has repeatedly been the subject of genetic studies to elucidate its prehistoric and historic demography. While some studies reported a genetic distinction between Northern and Southern Han Chinese, others showed a more clinal picture of small differences within China. Here, we investigated the distribution of Y chromosome variation along administrative as well as ethnic divisions in the mainland territory of the People's Republic of China, including 28 administrative regions and 19 recognized Chinese nationalities, to assess the impact of recent demographic processes. To this end, we analyzed 37,994 Y chromosomal 17-marker haplotype profiles from the YHRD database with respect to forensic diversity measures and genetic distance between groups defined by administrative boundaries and ethnic origin. We observed high diversity throughout all Chinese provinces and ethnicities. Some ethnicities, including most prominently Kazakhs and Tibetans, showed significant genetic differentiation from the Han and other groups. However, differences between provinces were, except for those located on the Tibetan plateau, less pronounced. This discrepancy is explicable by the sizeable presence of Han speakers, who showed high genetic homogeneity all across China, in nearly all studied provinces. Furthermore, we observed a continuous genetic North-South gradient in the Han, confirming previous reports of a clinal distribution of Y chromosome variation and being in notable concordance with the previously observed spatial distribution of autosomal variation. Our findings shed light on the demographic changes in China accrued by a fast-growing and increasingly mobile population.

Mayans: a Y chromosome perspective.

UNLABELLED: In spite of the wealth of available cultural and archeological information as well as general interest in the Mayans, little is known about their genetics. In this study, for the first time, we attempt to alleviate this lacuna of knowledge by comprehensively investigating the Y chromosome composition of contemporary Mayan populations throughout their domain. To accomplish this, five geographically targeted and ethnically distinct Mayan populations are investigated using Y-SNP and Y-STR markers. FINDINGS: overall, the Mayan populations as a group are highly homogeneous, basically made up of only two autochthonous haplogroups, Q1a2a1a1*-M3 and Q1a2a1*-L54. Although the Y-STR data illustrates diversity, this diversity, for the most part, is uniformly distributed among geographically distant Mayan populations. Similar haplotypes among populations, abundance of singletons and absence of population partitioning within networks among Mayan populations suggest recent population expansion and substantial gene flow within the Mayan dominion, possibly due to the development of agriculture, the establishment of interacting City-State systems and commerce.

Extreme genetic heterogeneity among the nine major tribal Taiwanese island populations detected with a new generation Y23 STR system.

The Taiwanese aborigines have been regarded as the source populations for the Austronesian expansion that populated Oceania to the east and Madagascar off Africa to the West. Although a number of genetic studies have been performed on some of these important tribes, the scope of the investigations has been limited, varying in the specific populations examined as well as the maker systems employed. This has made direct comparison among studies difficult. In an attempt to alleviate this lacuna, we investigate, for the first time, the genetic diversity of all nine major Taiwanese aboriginal tribes (Ami, Atayal, Bunun, Rukai, Paiwan, Saisat, Puyuma, Tsou and Yami) utilizing a new generation multiplex Y-STR system that allows for the genotyping of 23 loci from a single amplification reaction. This comprehensive approach examining 293 individuals from all nine main tribes with the same battery of forensic markers provides for the much-needed equivalent data essential for comparative analyses. Our results have uncovered that these nine major aboriginal populations exhibit limited intrapopulation genetic diversity and are highly heterogeneous from each other, possibly the result of endogamy, isolation, drift and/or unique ancestral populations. Specifically, genetic diversity, discrimination capacity, fraction of unique haplotypes and the most frequent haplotypes differ among the nine tribes, with the Tsou possessing the lowest values for the first three of these parameters. The phylogenetic analyses performed indicate that the genetic diversity among all nine tribes is greater than the diversity observed among the worldwide reference populations examined, indicating an extreme case of genetic heterogeneity among these tribes that have lived as close neighbors for thousands of years confined to the limited geographical area of an island.

Taiwanese aborigines: genetic heterogeneity and paternal contribution to Oceania.

In the present study, for the first time, 293 Taiwanese aboriginal males from all nine major tribes (Ami, Atayal, Bunun, Rukai, Paiwan, Saisat, Puyuma, Tsou, Yami) were genotyped with 17 YSTR loci in a attend to reveal migrational patterns connected with the Austronesian expansion. We investigate the paternal genetic relationships of these Taiwanese aborigines to 42 Asia-Pacific reference populations, geographically selected to reflect various locations within the Austronesian domain. The Tsou and Puyuma tribes exhibit the lowest (0.1851) and the highest (0.5453) average total genetic diversity, respectively. Further, the fraction of unique haplotypes is also relatively high in the Puyuma (86.7%) and low in Tsou (33.3%) suggesting different demographic histories. Multidimensional scaling (MDS) and analysis of molecular variance (AMOVA) revealed several notable findings: 1) the Taiwan indigenous populations are highly diverse. In fact, the level of inter-population heterogeneity displayed by the Taiwanese aboriginal populations is close to that exhibited among all 51 Asia-Pacific populations examined; 2) the asymmetrical contribution of the Taiwanese aborigines to the Oceanic groups. Ami, Bunun and Saisiyat tribes exhibit the strongest paternal links to the Solomon and Polynesian island communities, whereas most of the remaining Taiwanese aboriginal groups are more genetically distant to these Oceanic inhabitants; 3) the present YSTR analyses does not reveal a strong paternal affinity of the nine Taiwanese tribes to their continental Asian neighbors. Overall, our current findings suggest that, perhaps, only a few of the tribes were involved in the migration out of Taiwan.

Promoter polymorphisms of SERPINE1 are associated with the antidepressant response to depression in Alzheimer's disease.

Depression is one of the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). As the main regulator of the tissue plasminogen activator/brain-derived neurotrophic factor axis, plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of both AD and depression. This suggests a potential role of the PAI-1 gene SERPINE1 in the development of AD-related depression and its response to antidepressant treatment. The purpose of this study was to explore the association between the SERPINE1 promoter polymorphisms (rs1799889 and rs2227631) and the risk of depression in AD and to determine the relationship between these 2 polymorphisms and the response to paroxetine treatment in AD patients with depressive symptoms. A total of 423 AD patients, all of which were inpatients, including 161 patients with obvious depressive symptoms, were recruited into this study, and the MassARRAY system was used for genotyping. We failed to detect any significant associations of these 2 polymorphisms with AD-related depression in the Chinese population (p>0.05). However, for the depressive symptoms in AD, the frequency of the 5G allele of rs1799889 was significantly higher (p=0.009 after Bonferroni correction) in responders than in non-responders to an 8-week paroxetine treatment. Our preliminary results suggest that the SERPINE1 promoter polymorphisms may be associated with antidepressant treatment, but not with the increased susceptibility to the depressive symptoms in AD.

Evaluation of 96 SNPs in 14 populations for worldwide individual identification.

Great advances have been made recently in searching for individual identification single-nucleotide polymorphisms (IISNPs or IDSNPs). Such SNPs as suggested by SNPforID scientists and by Pakstis et al., are promising, although they were selected from older or smaller databases rather than the most recent database. Here, we describe a new computational strategy for developing IDSNPs based on HapMap. We searched through HapMap r27 for SNPs having minor allele frequencies ≥0.30 in all its 11 populations and found more than 1881 qualified SNPs. We examined 96 of them with 183 DNA samples from three Chinese populations using Illumina arrays. The average allele frequency for these 96 SNPs among the three populations was 0.495/0.505, the average number of identical SNP genotypes shared by two individuals among the 14 populations (three Chinese and 11 HapMap) was 37.9, and the random matching probability for two unrelated Hans to match in all 96 genotypes was 9.793 × 10(-39). Thus, most of these 96 SNPs are universally applicable.

[A study on paternity testing with 96 autosomal SNPs].

OBJECTIVE: To explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing. METHODS: All SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were ≥ 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)). RESULTS: Family 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869. CONCLUSION: When applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.

A study on the influence of ethanol over the primary cultured rat cortical neurons by using the scanning electron microscopy.

As an inhibitor and toxic factor of central nervous system, ethanol inhibits the action of the neurons and causes various kinds of neuronal damage. However, the precise mechanisms that ethanol-induced neuronal damage in the central nervous system remain unclear. In spite of thousands of published studies, little information is available on the neurons' morphological alteration in the central nervous system. In this study, we investigated the morphological alterations of the primary cultured rat cortical neurons after they were treated by different concentrations of ethanol using the scanning electron microscopy. Our results showed that the moderate or high concentration of ethanol could lead to morphological changes of these cultured rat cortical neurons, and they were closely associated with the duration of time. Our study will provide a new base for further studies on the effects of ethanol in the central nervous system.

Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population.

BACKGROUND: The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population. METHODS: Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases. RESULTS: rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12 - 26.67; P = 0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05 - 2.70; P = 0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13 - 4.94; P = 0.02) when compared with the wild haplotype. This association was not significant in male patients. CONCLUSIONS: The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.