A case of primary selective hypoaldosteronism carrying three mutations in the aldosterone synthase (Cyp11b2) gene

An infant with a clinical phenotype of early onset hypoaldosteronism has been screened for mutation analysis of the Cyp11b2 gene encoding aldosterone synthase enzyme. We have described a novel nonsense mutation in exon 3 (c.508C>T) that gave rise to a shorter protein (Q170X) and two known concurrent missense mutations (c.594A>C in exon 3 and c.1157T>C in exon 7) that led to substitution of glutamic acid for aspartic acid at amino acid position 198 (E198D) and of valine for alanine at amino acid position 386 (V386A). The father, who carried E198D plus V386A mutations, showed a fractional sodium excretion of 1.25% that was unmodified by dietary salt restriction, suggesting a mild haploinsufficiency. We examined by in silico analysis the effect of the mutations on the secondary and tertiary structures of aldosterone synthase to explain the inefficient enzymatic activity. The Q170X mutation produced a truncated protein, which was consequently associated with a loss of catalytic activity. As predicted by JPred web system and Dock 6.3 software, the concurrent expression of E198D and V386A mutations induced a significant secondary structure rearrangement and a shift of the heme group and the 18-hydroxycorticosterone substrate from their optimal placement.     

Association study of AGER gene polymorphism and hypertension in Han Chinese population

Background

Advanced glycation end products (AGEs) are produced by non-enzymatic glycation or glycoxidation of proteins, lipids and nucleic acids. The bond of AGEs and the receptor of AGE (AGER) in a pro-oxidant environment could induce immune and inflammation reaction involved in progress of microvascular disease. Accumulated evidence warrant further study on AGE–AGER pathway and genetic susceptibility to hypertension (HT).

Methods

We designed a two-stage association study to evaluate the association of AGER polymorphism and HT. In stage 1, seven tagSNPs were tested in 524 cases and 531 controls and the significant SNPs (P < 0.05) would enter into stage 2 including 807 cases and 869 controls. Furthermore, joint analysis was performed for all 2731 subjects including 1331 cases and 1400 controls, and meta-analysis was applied to evaluate combined estimations from the subgroups of stage 1 and stage 2.

Results

In stage 1, rs204994 had significant association with HT (P < 0.05) and enter stage 2. Neither joint analysis nor meta-analysis found statistical association of rs204994 with HT after adjusted for the covariates in the whole population. However, further stratification analysis found that rs204994 was significantly associated with HT in < 50 years and ≥ 50 years groups, ORs (95%CI) of dominant model were 1.623 (1.054–2.500) and 0.721 (0.546–0.952) respectively. No significant correlation was found between blood pressure and the polymorphisms of rs204994.

Conclusions

Our data suggests that age might modulate the genetic effects of variation of rs204994 in AGER on HT and further replications in other populations and functional studies should be warranted.     

Polymorphism of the methylenetetrahydrofolate reductase gene C677T and its influence on the antihypertensive and vascular protective effects of short-term lercanidipine treatment

Objective

To determine whether the antihypertensive and vascular protective effects of short-term treatment with lercanidipine, a calcium channel blocker, are modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.

Methods

In a self-controlled study, a total of 143 essential hypertensive patients, all permanent residents of Shanghai, were included. All of them were treated orally with lercanidipine at a single daily fixed dosage of 10 mg for 28 consecutive days and the genotypes of the MTHFR C677T polymorphism were determined. Blood pressures, ankle-brachial index values (ABI), and pulse wave velocity (PWV) were measured at baseline and on the 29th day.

Results

The 110 subjects for whom complete genotype and phenotype information were available were used for final data analysis. Patients with the TT genotype showed higher baseline diastolic blood pressure (DBP) than those with the CC and CT genotypes (P = 0.018). Within each genotype group, SBP, DBP and PWV showed significant difference between baseline and after treatment (P < 0.05). However, ABI showed significant difference between baseline and after treatment only within the CT and TT groups (P < 0.05) but not in the CC group (P > 0.05). Patients with the TT genotype presented a greater reduction in normalized PWV than those with the CC and CT genotypes (P = 0.02). Patients in all genotype groups had statistically similar changes in normalized SBP, DBP and ABI (P > 0.05).

Conclusion

The MTHFR gene polymorphism C677T might be associated with the vascular protective effects of short-term lercanidipine treatment. However, the MTHFR C677T polymorphism might not affect the antihypertensive effects of the lercanidipine treatment.     

Is there any association of apolipoprotein E gene polymorphism with obesity status and lipid profiles? Tehran Lipid and Glucose Study (TLGS)

Aims

Considering the key role played by the apolipoprotein E (Apo E) gene in the regulation of lipid metabolism and obesity, the current study has evaluate the association between abdominal obesity and Apo E gene polymorphism in a population of Tehran.

Materials and methods

A cross-sectional study was performed on 345 men and 498 women, aged 19–86 years, selected from among participants of the Tehran Lipid and Glucose Study. The RFLP-PCR technique was employed to investigate polymorphism in the gene fragments. Based on the national survey of risk factors for non-communicable diseases of Iran, waist circumference (WC) cut off was set at 89 cm for men and 91 cm for women. The risk effect of obesity related variables and lipid profiles in two groups of WC were examined by logistic regression. For body mass index (BMI), waist to hip ratio (WHR), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and blood pressure (BP), the standard risk cut-offs were applied.

Results

Frequencies of E2, E3, and E4 alleles were 9.7, 73, and 14.6%, respectively. The presence of the E3 allele was significantly associated with higher TG level in subjects with high WC, while, the presence of E4 allele decreased the plasma HDL-C (E2:52.1 ± 13.1 vs., E3:48.9 ± 11.2 vs., E4:44.6 ± 10.6 mg/dl, p < 0.05), HDL-C2 (E2:20.4 ± 9.2 vs., E3:19.1 ± 8.8 vs., E4:16.3 ± 7.9 mg/dl, p < 0.05), and HDL-C3 (E2:32.1 ± 7.4 vs., E3:30.3 ± 6.2 vs., E4:28.3 ± 6.1 mg/dl, p < 0.05) in normal WC subjects. The presence of the E3 carrier increased the risk of having higher plasma TG, compared with the E2 carrier (95% CI OR = 1.91, 1.02–3.57; p = 0.04).

Conclusion

According to the results of this study, the E3 carrier, caused an approximately 90% increase in the levels of TG in the group with abdominal obesity.     

Vertebrate evolution reflected in the evolution of nuclear ribosomal internal transcribed spacer 2

Plastics are widely used in modern life, and their unbound chemicals bisphenol A and phthalates can leach out into the surrounding environment. BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects. In The Comparative Toxicogenomics Database, BPA and five most frequently curated PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to have 1932 and 484 interactions with genes/proteins, respectively. Five of their top ten toxicity networks were found to be involved in inflammation, and their top ten diseases included genital, prostatic, endomentrial, ovarian and breast diseases. BPA and PAEs were found to exhibit similar toxicogenomics and adverse effects on human health owning to their 89 common interacting genes/proteins. These 89 genes/proteins may serve as biomarkers to assay the toxicities of different chemicals leached out from the widely used plastics.     

利用序列比较寻找胰岛素基因表达启动区与DNA结合蛋白的结合位点

NDFl、IPFl和HNF4是与胰岛素基因表达有关的DNA结合蛋白,通过比较SWISSPROT蛋白质数据库中人类、小鼠、大鼠这三种核蛋白氨基酸一级序列、模体和结构域,发现其结构十分相似,根据蛋白质结构和功能的关系,推测这些DNA结合蛋白与胰岛素基因结合的核苷酸序列相似;从GenBanl(核酸数据库中获得人类、小鼠、大鼠胰岛素DNA序列,用ClustalW比较三者Promoter区的核苷酸序列,显示有一段核苷酸序列较为相似,同时搜索TRANSFAC基因转录数据库中NDFl、IPFl和NHF4蛋白核苷酸结合位点,发现核酸比对保守的部分序列与TRANSFAC数据库中这三个转录因子的DNA结合位点一致,另外一些核酸保守序列可能为其他未知DNA结合蛋白的结合位点。这种核酸序列比对设计为分子生物学实验寻找和验证胰岛素DNA结合蛋白与核苷酸的结合位点提供了简单而实用的方法。     

BBP、DBP、BPA、NP对鸡胚胎生殖腺发育的影响

雌性荷尔蒙已烯雌酚(Diethylstilbestrol,DES)可以导致鸡受精卵雌性化,为了明确环境荷尔蒙疑似物邻苯二甲酸丁酯苯甲酯(Butyl benzyl phthalate,BBP)、邻苯二甲酸二丁酯(Dibutyl phthalate,DBP)、双酚A(Bisphenol A,BPA)、壬基酚(Nonyl Phenol,NP)是否和DES一样具有雌性荷尔蒙的作用,本研究以不同浓发的BBP、DBP、BPA、NP注射到鸡的受精卵内,观察生殖腺的发育及其受到的影响.结果 表明:BBP导致雌性雏鸡的生殖腺重量显著增加;DBP、BPA、NP对鸟类生殖腺的发育没有显著影响;BBP、DBP、BPA、NP没有出现与DES类似的雌化现象;不能引起雄性个体的雌性化.     

好氧条件下Sphingomonassp.XJ1降解DBP途径的研究

在三角瓶中采用Sphingomonas sp.XJ1对邻苯二甲酸丁酯(DBP)进行好氧降解,以考察DBP的降解途径。分别对降解16h、32h和40h的DBP样品进行代谢产物分析,可判定保留时间为4.79min和5.11min所对应的代谢产物分别为原儿茶酸和邻苯二甲酸。由此可知,菌株Sphingomonas sp.XJ1对DBP的降解遵循DBP好氧生物降解途径的一般途径。即在菌株XJ1的作用下,DBP首先水解为MBP,继而水解为PA,经由PCA最终完全降解为CO2和H2O。     

The Group-Specific Component/Vitamin D Binding Protein (GC/DBP) in Jewish Population Groups. Distribution of common and rare alleles. Description of a new variant GC1C51

The distribution of GC phenotypes and alleles was determined in six Jewish population groups from Israel. In Jews of eastern Europe, central Europe and North Africa, the allele distribution was similar to that of European non-Jewish populations. GC^*2 frequencies were considerably lower in Jews of the Middle East and highest in Jews of the Balkan area (Rumania and Bulgaria). A new rare GC variant allele, hitherto not encountered, was observed in six Jewish individuals of various countries of origin. This variant was classified as GC 1C51.