Association of Lymphotoxin Alpha Polymorphism with Type 1 Diabetes in a Tunisian Population

We investigated the association of the lymphotoxin (LT)-α gene polymorphism +249A/G with type 1 diabetes. The distribution of genotypes of the LT-α +249A/G single nucleotide polymorphism (SNP) was assessed in 115 diabetic patients and 123 normoglycemic control subjects, using PCR-restriction fragment length polymorphism analysis. Among unselected patients, the SNP was significantly associated with increased risk of diabetes (χ² = 8.44, p = 0.014) and was found to be more pronounced among female (χ² = 8.37, p = 0.02) than male (χ² = 6.11, p = 0.047) patients. A significant association was detected between LT-α +249A/G and increased risk of diabetes, in particular for young-onset patients (χ² = 6.92, p = 0.031). Moreover, we reported significant differences in levels of HbA1c, triglycerides, alanine transaminase, and anti-glutamic acid decarboxylase-65 among alleles. Additional studies with extended patient age groups and different ethnicities are needed to confirm our findings.     

Subcultural Variations in an Urban Poor Population

The assumption that the poor constitute a subsociety with a homogeneous subculture is examined empirically in an urban poverty sample. The existence of subcultural differences in the sample was tested by using a number of criteria that have been suggested for classifying cultural systems. The data indicate that for the sample studied there are two subcultures–one Black and one White. A hypothesis for the development and persistence of subcultural variations is proposed. The research which is reported and that which is suggested is seen as a necessity for providing an objective basis for the structuring of domestic social change programs.     

DNA Polymorphism in Population Genetics

In the review, the literature evidence on DNA polymorphism obtained in the last 10–15 years using various molecular-genetic methods is summarized. All main types of DNA variation are considered but attention is focused on those extensively used in population genetics. The areas of using DNA markers are outlined and the limitations of their potential in analyzing genetic processes in populations are discussed. Particular emphasis is placed on the relationship between the earlier developed biochemical genetics based on protein polymorphism analysis and modern molecular population genetics based on DNA polymorphism. The possible role of selection in maintaining DNA variation is considered.     

Heterozygote Advantage Probably Maintains Rhesus Factor Blood Group Polymorphism: Ecological Regression Study

Rhesus factor polymorphism has been an evolutionary enigma since its discovery in 1939. Carriers of the rarer allele should be eliminated by selection against Rhesus positive children born to Rhesus negative mothers. Here I used an ecologic regression study to test the hypothesis that Rhesus factor polymorphism is stabilized by heterozygote advantage. The study was performed in 65 countries for which the frequencies of RhD phenotypes and specific disease burden data were available. I performed multiple multivariate covariance analysis with five potential confounding variables: GDP, latitude (distance from the equator), humidity, medical care expenditure per capita and frequencies of smokers. The results showed that the burden associated with many diseases correlated with the frequencies of particular Rhesus genotypes in a country and that the direction of the relation was nearly always the opposite for the frequency of Rhesus negative homozygotes and that of Rhesus positive heterozygotes. On the population level, a Rhesus-negativity-associated burden could be compensated for by the heterozygote advantage, but for Rhesus negative subjects this burden represents a serious problem.     

Prevelence of Primary Aldosteronism in an Urban Hypertensive Population

Objective: To determine the prevalence of primary aldosteronism (PA) in hypertensive patients presenting to the primary care clinic at The Mount Sinai Hospital, regardless of the degree of hypertension and to identify clinical criteria that should prompt screening for PA.Methods: An aldosterone:renin ratio (ARR, cutoff ≥20, with plasma aldosterone concentration [PAC] ≥10 and suppressed renin) was used to prospectively screen 296 hypertensive patients (blood pressure [BP] ≥140/90) over the age of 18 from August 2012 through May 2013. Subjects who screened positive then underwent confirmatory oral salt load testing (OSLT).Results: Of the 296 patients, 14 screened positive for PA, an overall prevalence of 4.7%. Six of the 14 cases underwent confirmatory OSLT, upon which 2 were confirmed positive, for a prevalence of 0.7%. Overall, patients with confirmed PA were more likely to have resistant hypertension (42.9% vs. 18.1% (P =.0334)) and require more antihypertensive agents (2.8 ± 1.2 agents vs. 2.1 ± 1.1 agents, P =.0213). There was a trend toward lower potassium values in the cases.Conclusion: The prevalence of PA in our clinic is much lower than in reports from certain “at-risk” populations. PA screening is indicated in patients with resistant hypertension, regardless of serum potassium levels.Abbreviations:ARR = aldosterone:renin ratioACTH = adrenocorticotropic hormoneAVS = adrenal venous samplingBP = blood pressureMRA = mineralocorticoid receptor antagonistOSLT = oral salt load confirmatory testPA = primary aldosteronismPAC = plasma aldosterone concentrationPCP = primary care providerPRA = plasma renin activity     

Influence of the C242T Polymorphism of the p22-phox Gene (CYBA) on the Interaction between Urinary Sodium Excretion and Blood Pressure in an Urban Brazilian Population

Background

Reactive oxygen species are implicated in the physiopathogenesis of salt-induced hypertension and the C242T polymorphism of the p22-phox gene has been associated with higher superoxide production. This study investigated the impact of this polymorphism on the relationship between urinary sodium excretion (USE) and blood pressure levels in an urban Brazilian population.

Methods

We cross-sectionally evaluated 1,298 subjects from the city of Vitoria-ES, located in the Southeast region of Brazil, by clinical history, physical examination, anthropometry, analysis of laboratory parameters, USE measurement and p22-phox C242T polymorphism genotyping.

Results

No significant differences in studied parameters were detected between the studied genotype groups (CC vs. CT+TT). Systolic blood pressure exhibited significant correlation with USE only in T allele carriers (r = 0.166; p<0.001), while diastolic blood pressure and hypertension status correlated with USE in both genotypes albeit more weakly in subjects with CC genotype (r = 0.098; p = 0.021 and r = 0.105; p = 0.013, respectively) than in T carriers (r = 0.236; p<0.001 and r = 0.213; p<0.001, respectively). Regression analyses adjusted for confounding factors showed that USE remained independently associated with systolic (p<0.001) and diastolic blood pressure (p<0.001) and hypertension status (p = 0.004) only in T allele carriers. Finally, higher diastolic and systolic blood pressure levels were detected in T allele carriers than in CC genotype individuals in the highest tertile of USE.

Conclusions

The p22-phox 242T allele is associated with higher blood pressure levels among subjects with higher USE in an urban Brazilian population.     

中国汉族群体(西安)DNA HaeⅢ系统遗传多态性

建立了Ｄ２Ｓ９２、Ｄ２Ｓ４４、Ｄ１０Ｓ２８、Ｄ１７Ｓ７９ ４个位点的荧光检测ＲＦＬＰ技术,准确、快速、安全。同时,对尼龙膜ＤＮＡ固定、剥脱尼龙膜再杂交进行了实验,结果表明,碱性磷酸酶标记寡核苷酸探针和荧光检测技术具有很高灵敏度和稳定性,检测样本ＤＮＡ的最小量约３－２５ｎｇ。它将在法医鉴定、基因诊断和遗传研究等领域中发挥越来越大的作用。采用严格地随机抽样,对西安汉族群体进行遗传学调查,用ＡＬＩ８７４     

Molecular Diagnostic and Prognostic Subtyping of Gliomas in Tunisian Population

It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.     

新疆维吾尔族HLA-Cw基因座遗传多态性调查 The Study of HLA-Cw Polymorphism in Uygur Population

采用序列特异性寡核苷酸探针杂交技术（PCR-SSOP）对146位新疆维吾尔族无关个体HLA-Cw基因座进行基因分型,研究该民族HLA-Cw基因座遗传多态性,建立新疆维吾尔族HLA-Cw基因频率数据库。检出18种等位基因,基因频率分布在0.0069~02460,其中HLA-Cw*04、07、08、14基因频率比较高,基因频率分别为02460、0.1151、0.1010、0.1202,共占新疆维吾尔族可检出等位基因的58.23%,PCR-SSOP分型技术使新疆维吾尔族HLA-Cw基因座空白基因频率降至0.0064。经χ2检验,基因型分布符合Hardy-Weinberg平衡定律。建立民族HLA-Cw基因座基因频率数据库,为临床器官移植配型、人类学、法医学提供重要的群体遗传学资料。 Abstract:The HLA-Cw loci polymorphism in Uygur population was investigated using the PCR- sequence specific oligonucleotide probe (SSOP) method,and the genetic database on the distribution of gene frequency of the HLA-Cw loci was established.From 146 individuals of Uygur population,18 HLA-Cw alleles were detected.The gene frequency was from 0.0069 to 0.2460.The four most common alleles were HLA-Cw*04(24.60%)、07(11.51%)、08(1010%)、14(12.02%),and they covered 58.23% of total alleles detected from Uygur population.We have made a survey of HLA-Cw alleles frequencies in a Uygur population,with blank frequency being lowered to 0.0064.The distribution of genotype frequencies met the law of Hardy-Weinberg equilibrium by hi-square test.The frequency data can be used in forensic and paternity tests to estimate the frequency of a DNA profile in the Uygur population,transplant matching and anthropology.     

Asthma Is Inversely Associated with Helicobacter pylori Status in an Urban Population

Background

Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma.

Methods

Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured.

Results

As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36–0.89). Median age of onset of asthma (doctor''s diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006).

Conclusion

These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00212537","term_id":"NCT00212537"}}NCT00212537     

A Viable Population of the European Red Squirrel in an Urban Park

Whether urban parks can maintain viable and self-sustaining populations over the long term is questionable. In highly urbanized landscapes, urban parks could play a role in biodiversity conservation by providing habitat and resources to native species. However, populations inhabiting urban parks are usually small and isolated, leading to increased demographic stochasticity and genetic drift, with expected negative consequences on their viability. Here, we investigated a European red squirrel population located in an urban park close to Paris, France (Parc de Sceaux; 184 ha) to assess its viability. Using mitochondrial D-loop sequences and 13 microsatellite loci, we showed that the population presented high levels of genetic variation and no evidence of inbreeding. The size of the population was estimated at 100–120 individuals based on the comparison of two census techniques, Distance Sampling and Capture-Mark-Recapture. The estimated heterozygosity level and population size were integrated in a Population Viability Analysis to project the likelihood of the population''s persistence over time. Results indicate that the red squirrel population of this urban park can be viable on the long term (i.e. 20 years) for a range of realistic demographic parameters (juvenile survival at least >40%) and immigration rates (at least one immigration event every two years). This study highlights that urban parks can be potential suitable refuges for the red squirrel, a locally threatened species across western European countries, provided that ecological corridors are maintained.