Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

Mitochondrial complex I deficiency has been implicated in the pathogenesis of Parkinson’s disease (PD), but as yet no mitochondrial DNA (mtDNA) variations have been identified that could account for the impaired complex I activity. On the other hand, it has been suggested that mtDNA polymorphisms (mtSNPs) or haplogroups may modify the risk of developing PD. Here, we determined the distributions of ten mtSNPs that define the nine major European haplogroups among 224 PD patients and 383 controls from Crete, an island of 0.6 million inhabitants who share a similar genetic background and a common environment. The recruitment of patients and controls was restricted to individuals of Cretan origin for at least three generations from both parental sides in order to avoid population admixture and subsequent genetic heterogeneity. We found no mtSNP or mtDNA haplogroup that predisposes to PD, although there was a trend for haplogroups J, T, U and I and the supercluster of haplogroups UKJT to be slightly underrepresented in our PD patients as compared to controls. While a combination of common mtSNPs (present in ≥5% of the general population) may decrease the chance of developing PD, this effect was minor in the Cretan population.     

CYP 17 and estrogen receptor α gene polymorphisms: association with breast cancer susceptibility and clinicopathological parameters in a cohort of Egyptian patients

The association between exposure to endogenous and exogenous steroid hormones and breast cancer (BC) risk is well established. The aim of this study was to examine whether Cytochrome P450 (CYP)17 -34T>C and estrogen receptor (ER)α XbaI gene polymorphisms might influence endogenous estrogen hormone level. Also, we aimed to examine the potential association between these polymorphisms and BC risk, as well as some clinicopathological parameters in BC patients. Eighty-one Egyptian female subjects were recruited; 41 pathologically confirmed BC patients and 40 apparently healthy, age-matched female control subjects. Serum estradiol level was assayed using radioimmunoassay. Polymerase chain reaction–restriction fragment length polymorphism technique was used for detection of CYP 17 -34T>C and ERα-XbaI polymorphisms. Serum estradiol level did not show statistically significant difference when compared between the different CYP17 and ERα genotypes in controls (p?=?0.088 and 0.241, respectively). No significant association between CYP17 and ER α gene polymorphisms and BC risk was encountered. There was a statistically significant association between ER α genotypes in overall BC cases with each of age at menarche, p?=?0.024, age at diagnosis, p?=?0.011, and nodal involvement, p?=?0.037, and between nodal number and ER α genotypes in the premenopausal BC group, p?=?0.038. In conclusion, CYP17 and ERα genotypes did not influence serum estradiol level. No statistically significant association was found between CYP17 -34T>C and ERα XbaI gene polymorphisms and breast cancer risk in Egyptian women. ER α gene may have an association with some clinicopathological parameters in breast cancer in Egyptian patients.     

FCεRI gene promoter polymorphisms and total IgE levels in susceptibility to atopic dermatitis in Korea

IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (FcεRI) is involved in the pathogenesis of allergen-induced immune responsiveness in atopic diseases like atopic dermatitis (AD). We sought to determine FcεRI gene polymorphisms are associated with AD in Korean patients, and analyzed the relevance of FcεRI gene polymorphisms and serum IgE levels. We conducted a case-control association analysis (175 patients and 56 controls) of Korean subjects. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay, and serum levels of IgE were measured using a fluorescence enzyme immunoassay. We found that there were no significant relationships between FcεRI and AD, although there were trends towards an association between the 66T>C (rs2251746) polymorphism and total serum IgE levels in the Korean AD patients. In conclusion, while the 66T>C (rs2251746) of the FcεRIα polymorphism may be linked to AD and higher serum IgE levels, polymorphisms in the FcεRIβ gene did not confer susceptibility to AD in our patient sample.     

Association of genetic variants in estrogen receptor α with HCV infection susceptibility and viral clearance in a high-risk Chinese population

The purpose of this study was to test the hypothesis that genetic variants of estrogen receptor α (ERα) are associated with the outcomes of hepatitis C virus (HCV) infection. We genotyped the seven single nucleotide polymorphisms (SNPs) (rs2077647, rs9340799, rs2234693, rs1801132, rs9322354, rs2228480 and rs3798577) of ERα and conducted a case-control study in a high-risk Chinese population, including 429 HCV spontaneous clearance cases, 880 persistent infection cases and 1,174 uninfected controls. The C allele of rs2234693 was significantly associated with increased susceptibility to HCV infection [dominant model: adjusted odds ratio (OR)?=?1.377, 95 % confidence interval (CI) =1.126–1.778], and the risk effect remained significant among the younger (≤55 years) and hemodialysis subjects (all P?<?0.007). The other three SNPs variant genotypes also showed significant correlation with elevated risk of HCV infection in different strata (rs2077647 in males; rs9340799 in blood donors; rs1801132 in younger subjects; all P?<?0.007). It was also discovered that carriage of rs2228480 A allele was more prone to develop persistent HCV infection (dominant model: adjusted OR?=?1.203, 95 % CI?=?1.154–1.552), and the risk effect was more evident in females and blood donors (all P?<?0.007). Haplotype analyses (rs2077647, rs9340799 and rs2234693) showed that, compared with the most frequent haplotype TAT, CAC played a risk effect in subgroups of younger (P?=?3.24?×?10^?3) and male (P?=?5.51?×?10^?4), whereas CAT expressed a protective effect in females (P?=?2.27?×?10^?4) for HCV infection susceptibility. We first report that these SNPs (rs2077647, rs9340799, rs2234693, rs1801132 and rs2228480) in ERα can influence the outcomes of HCV infection in a high-risk Chinese population.     

Relationship between single nucleotide polymorphisms in the 3’-untranslated region of the vascular endothelial growth factor gene and susceptibility to diabetic peripheral neuropathy in China

Introduction

This study is to elucidate the relationship between a 936C/T mutation at the 3’-untranslated region of the human vascular endothelial growth factor (VEGF) gene and diabetic peripheral neuropathy (DPN).

Material and methods

All subjects recruited in this study were divided into DM (diabetes without neuropathy, retinopathy or nephropathy), DPN (diabetes with peripheral neuropathy only) and healthy control groups. The gene polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism, as well as other clinical methods including serum VEGF by ELISA.

Results

The C allele frequency and CC genotype frequency in the DPN group were higher than those in the NC group and DM group. The T allele frequency and CT+TT genotype (carrying the T allele) frequency in the DPN group were lower than those in the NC group (χ² = 19.051 and 18.533, both p < 0.001) and DM group (χ² = 11.117 and 11.156, both p = 0.001). However, there was no statistically significant difference in the three genotype (CC/CT+TT) frequencies and allele (C/T) frequencies between the DM group and the NC group. The multivariate logistic regression analysis showed that the levels of glycated hemoglobin (HbA_1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and plasma VEGF positively correlated with DPN, while the 936C/T gene polymorphism of VEGF negatively correlated with DPN.

Conclusions

Allele 936C of VEGF may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.     

Behçet's disease exhibits an increased osteopontin serum level in active stage but no association with osteopontin and its receptor gene polymorphisms

Osteopontin (OPN) and its receptors have been reported to be involved in a number of autoimmune and inflammatory diseases. This study was designed to analyze the OPN serum level in Behçet's disease (BD) and the association of gene polymorphisms of OPN and its receptors with BD. The serum level of OPN in active BD patients, inactive BD patients, and controls was assayed by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms (SNPs) of OPN and 4 SNPs of OPN receptors were genotyped in 318 BD patients and 313 controls using a polymerase chain reaction restriction fragment length polymorphism assay. The OPN level was significantly increased in the serum of active BD patients compared with inactive BD patients and controls. SNP analysis indicated an increased frequency of the OPN rs1126772 A allele in BD patients compared with controls. However, the significance was lost after Bonferroni correction. The prevalence of other SNPs of OPN and its receptors did not differ between BD patients and controls. The results suggest that an increased serum OPN level was associated with clinical severity of BD. There was no association of the tested SNPs of OPN and its receptors with BD in Chinese Han patients.     

Association between rs6887695 and 3′-untranslated region polymorphisms within the interleukin-12B gene and susceptibility to autoimmune diseases in Asian and European population: A meta-analysis

Background: The associations between rs6887695 and 3′-untranslated region (3′-UTR) single-nucleotide polymorphisms (SNPs) within interleukin-12B (IL-12B) and autoimmune diseases (ADs) remain controversial and inconclusive. The aim of this study was to evaluate the association between IL-12B (3′-UTR A/C and rs6887695 C/G SNPs) and ADs by meta-analysis. Methods: PubMed and EMBASE were exhaustively searched for studies on the association between IL-12B SNPs and ADs. Publication bias was examined by a funnel plot and Egger’s test. The robustness of the pooled results was assessed by sensitivity analysis. A fixed- or a random-effects model was applied to calculate the pooled odds ratios (ORs). Results: A total of 34 studies were included in this meta-analysis. The pooled results demonstrated that IL-12B rs6887695 SNPs were significantly associated with the risk of ADs. However, there was no significant association between IL-12B 3′-UTR SNPs and ADs. When the studies were stratified by ethnicity, significant association between IL-12B 3′-UTR SNPs and ADs was observed in both Asian and European population. In addition, allele A within 3′-UTR of IL-12B gene was found to be a protective factor for T1DM, but a risk factor for psoriasis. Conclusion: The IL-12B 3′-UTR and rs6887695 SNPs are associated with susceptibility to ADs.     

Hepatitis C virus RNA quantitation in a nationwide French cohort of patients co-infected with HIV and HCV: should the same test be applied to all samples?

In the ANRS CO13 HEPAVIH Cohort, HCV RNA measurement was performed with one of the two available real-time PCR assays [Roche Cobas AmpliPrep-Cobas TaqMan HCV (CAP-CTM) and the Abbott Real-Time HCV (ART)], according to the assay used in each center. To comply with the recommendations for using the same assay in multicenter clinical trials, all the 204 samples analyzed with ART were retested retrospectively by CAP-CTM. The aim of this study was to assess the usefulness of this strategy in real-life situations. A significant and positive correlation was observed between HCV RNA levels measured in the same samples with ART and CAP-CTM with all the genotypes tested. However, in 33 of the 204 (16%) clinical samples, the individual difference between HCV RNA levels measured by both assays was above ±0.5 log(10)IU/ml. Such viral load variations above 0.5 log(10) should be considered as significant. HCV RNA levels estimated by CAP-CTM for genotype 4 were significantly lower than those for genotypes 1, 2, and 3 (P<0.0001). This study shows that using the same assay in multicenter trials and cohorts is still relevant due to inter-assay differences observed in HCV plasma load measurements.     

The XmnI polymorphic site 5’ to the gene Gγ in a Brazilian patient with sickle cell anaemia – fetal haemoglobin concentration,haematology and clinical features

We report a 20-year-old female with sickle cell anaemia and with an HbF concentration of 15.8%. The patient was not using hydroxyurea and was not receiving regular blood transfusions. The patient never had chronic manifestations of sickle cell anaemia, only pain crises of a mild intensity. After laboratory tests, we found that she was homozygous for HbS with the Bantu/atypical haplotype, and was heterozygous for the XmnI site. The influence of the XmnI site on the expression of HbF can explain the amelioration in clinical features in this haplotype association in a case of sickle cell anaemia.     

Association of the C–509→T polymorphism, alone or in combination with the T869→C polymorphism, of the transforming growth factor-β1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women

Transforming growth factor-beta1 is an important local regulator of bone metabolism, acting downstream of estrogen and cooperatively with vitamin D. The possible association of a C 509-->T polymorphism in the promoter region of the transforming growth factor-beta1 gene, alone or in combination with a T869-->C (Leu10-->Pro) polymorphism, with bone mineral density and genetic susceptibility to osteoporosis was investigated in 625 postmenopausal Japanese women. The frequencies of the CC, CT, and TT genotypes of the C-509-->T polymorphism in the study population were 24%, 49%, and 27%, respectively. A significant association of C-509-->T genotype with bone mineral density was detected: lumbar spine (L2-L4) and total body bone mineral density values were 7% and 5% lower, respectively, in individuals with the TT genotype than in those with the CT or CC genotype. The serum concentration of transforming growth factor-beta1 did not vary with C-509-->T genotype. Multivariable logistic regression analysis, with adjustment for age, height, body weight, time since menopause, smoking status, body fat mass, and lean mass, revealed a significantly higher frequency of the TT genotype of the C-509-->T polymorphism in 286 individuals with osteoporosis than in 170 normal controls. Analysis of combined C-509-->T and T869-->C genotypes showed that L2-L4 bone mineral density decreases and the prevalence of osteoporosis increases with the number of T alleles. These results suggest that the C-509-->T polymorphism, alone or in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene is a genetic determinant of bone mass, and that the number of T alleles in the combined genotype is a risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women.