Common Variants Related to Serum Uric Acid Concentrations Are Associated with Glucose Metabolism and Insulin Secretion in a Chinese Population

Background

Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion.

Method

We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined.

Results

SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively).

Conclusions

Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.     

A Common Variant Of Ubiquinol-Cytochrome c Reductase Complex Is Associated with DDH

Purpose

Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH.

Methods

We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).

Results

In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10^-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10^-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10^-6 with the odds ratio of 1.35 (1.19–1.53) for allele A.

Conclusion

Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.     

Quantitative variability of 342 plasma proteins in a human twin population

The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies.     

水肥互作对滴灌玉米氮素吸收、水氮利用效率及产量的影响

优化水、氮供应是实现作物高产与水肥资源高效利用的有效途径.本文研究了田间试验条件下,水(4500、6750、9000 m³·hm^-2)、氮(0、225、330、435、540 kg·hm^-2)互作对高密度(≥105000 株·hm^-2)滴灌玉米干物质积累、氮素吸收及产量的影响.结果表明: 玉米干物质积累与吸氮量均随灌溉和施氮水平的增加明显升高,当施氮量大于435 kg·hm^-2和灌溉量大于9000 m³·hm^-2时则呈减少趋势.完熟期玉米干物质积累对灌水的响应表现为W₆₇₅₀(36359 kg·hm^-2)>W₉₀₀₀(35077 kg·hm^-2)>W₄₅₀₀(33451 kg·hm^-2),施氮对玉米吸氮量的变化表现为N₄₃₅(459.9 kg·hm^-2)>N₅₄₀(458.1 kg·hm^-2)>N₃₃₀(416.3 kg·hm^-2)>N₂₂₅(351.3 kg·hm^-2),N₄₃₅比N₃₃₀、N₂₂₀分别升高9.1%、32.7%,N₅₄₀比N₄₃₅降低0.6%.在施氮量0～435 kg·hm^-2范围内,玉米最大氮素吸收速率随施氮量增加而升高,在施氮量为435 kg·hm^-2时达最大(6.57 kg·hm^-2·d^-1).灌水与施氮均可显著增加玉米产量、穗粒数和穗粒质量,二者有明显的正交互作用,且以氮为主效应.在施氮0～435 kg·hm^-2范围内,氮肥利用率随施氮量的增加而升高,此后反而降低;灌溉水分生产率随施氮量升高而增加,随灌水量增加而明显下降,灌溉定额为4500～6750 m³·hm^-2时,灌溉水分生产率可达2.57～3.80 kg·m^-3.玉米最高产量18072 kg·hm^-2的施氮量为567.0 kg·hm^-2.最佳经济施氮量为427.9～467.7 kg N·hm^-2时,玉米产量在17109～17138 kg·hm^-2,氮素偏生产力和氮肥利用率分别达122 kg N·hm^-2和45.0%.水氮一体化施肥可实现滴灌玉米高产协同水、氮利用效率的共同提高.     

Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection

Background

Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).

Results

There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10⁻⁴), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10⁻⁴).

Conclusions

The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0121-7) contains supplementary material, which is available to authorized users.     

Profiling of Volatile Compounds and Associated Gene Expression and Enzyme Activity during Fruit Development in Two Cucumber Cultivars

Changes in volatile content, as well as associated gene expression and enzyme activity in developing cucumber fruits were investigated in two Cucumis sativus L. lines (No. 26 and No. 14) that differ significantly in fruit flavor. Total volatile, six-carbon (C6) aldehyde, linolenic and linoleic acid content were higher during the early stages, whereas the nine-carbon (C9) aldehyde content was higher during the latter stages in both lines. Expression of C. sativus hydroperoxide lyase (CsHPL) mirrored 13-hydroperoxide lyase (13-HPL) enzyme activity in variety No. 26, whereas CsHPL expression was correlated with 9-hydroperoxide lyase (9-HPL) enzyme activity in cultivar No. 14. 13-HPL activity decreased significantly, while LOX (lipoxygenase) and 9-HPL activity increased along with fruit ripening in both lines, which accounted for the higher C6 and C9 aldehyde content at 0-6 day post anthesis (dpa) and 9-12 dpa, respectively. Volatile compounds from fruits at five developmental stages were analyzed by principal component analysis (PCA), and heatmaps of volatile content, gene expression and enzyme activity were constructed.     

血管生成拟态和E-cad在食管鳞状细胞癌中的表达及临床意义

目的 探讨血管生成拟态( vasculogenic mimicry,VM)与E-钙粘蛋白(E-cadherin,E-cad))在食管鳞癌(esophageal squamous cell carcinoma)组织中的表达及意义.方法 收集食管鳞状细胞癌术后标本100例和30例癌旁正常食管黏膜,应用免疫组化法和组织化学法检测食管鳞状细胞癌和正常食管黏膜组织中VM和E-cad的表达情况.结果 在食管鳞状细胞癌组织和正常食管黏膜组织中,VM和E-cad的阳性表达率分别为47.0％、48.0％和0％、70.0％,差异有统计学意义(P＜0.05);VM及E-cad的表达与食管鳞癌的组织学分级、临床分期及淋巴结转移(P＜0.05);VM与E-cad在食管鳞癌中的表达呈负相关(r=-0.865,P=0.000).多因素分析:PTNM分期、淋巴结转移、VM和E-cad的表达是影响食管鳞癌根治术后患者预后的独立因素(P＜0.05);VM阳性组与阴性组的5年生存率分别为4.3％和64.2％,,差异有统计学意义(P=0.000);E-cad阳性组与阴性组5年生存率分别为60.4％和15.4％,差异有统计学意义(P=0.000).结论 具有VM结构的食管鳞状细胞癌的分化程度低,恶性度高,预后差,VM和E-cad表达的程度与食管鳞状细胞癌的进展和预后密切相关.     

利用ES细胞建立可诱导的白血病模型

胚胎干细胞（embryonic stem cells,ESCs）是从囊胚的内细胞团分离出来的多潜能干细胞,具有多向分化的能力。将外源基因导入ES细胞建立转基因动物,对于研究外源基因的功能和调控具有一定的价值。载有外源性基因的病毒在感染ES细胞后,可通过囊胚注射获得具有胚系遗传的该转基因动物,并且这一外源基因可以稳定遗传和表达。该研究主要是利用携带hPML-RARα基因的慢病毒感染小鼠ES细胞系（R1）,获得携带该基因的ES细胞,感染后的ES细胞核型正常。在此基础上,将感染后的ES细胞经囊胚注射,获得了携带有hPML-RARα基因的3只嵌合小鼠,其中,有1只具有遗传特性。对嵌合体小鼠与C57杂交的后代给予强力霉素（doxycycline）处理,3天以后骨髓细胞hPML-RARα基因开始表达,这证明了在小鼠体内该外源基因表达的可诱导性。以上证实,已经成功利用ES细胞建立了可诱导的白血病转基因小鼠模型。     

研究生病理学实验带教的探索与实践

医学研究生教育的目的是培养高素质创新型医学人才,创新离不开科研,病理学是多学科科研究工作的基础。建立科研平台提高科研能力是研究生教育十分关注的问题。如何培养研究生病理学实验能力,使学到知识技术在今后的科研活动中得以运用,本文就近几年我们在研究生病理学实验带教实践过程中的一些方法作一介绍。