PP Genotype Research Articles

Correlation between ERα gene polymorphism and multiple sclerosis and neuromyelitis optica.

Objective:To study the polymorphism distribution of estrogen receptor (ER) α gene and the correlation between different types of polymorphism in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients.Methods:Forty-six cases of MS and NMO diagnosed from June 2018 to December 2019 were collected. Peripheral venous blood samples were collected. The patient’s gender, age of onset, course of disease, and other clinical data were recorded. Fifty-eight healthy volunteers of the same age and sex were selected. By means of Pvu II and Xba I restriction fragment length polymorphism enzyme recognition sites of ER α gene, polymerase chain reaction-restriction fragment length polymorphism analysis was conducted.Results:There was no significant difference in the frequency distribution of ER α gene’s PP, Pp, and pp genotype between MS and NMO case group and control group (P = .598). Frequency distribution of ER α gene’s XX, Xx, and xx was statistically significant between MS and NMO case group and control group (P = .021). Among them, distribution of Xx and Xx gene frequency between patient group and the control group was statistically significant (P = .001, OR = 4.622, 95% CI: 1.803–11.852). There was no significant correlation between ER α genotypes and the onset age in patient group (P > .05). The difference was statistically significant in disease duration of XX and Xx genotype (P = .006). The comparison of Xx and xx genotype frequency distribution in gender exists a difference(P = .047, OR = 7.500, 95% CI: 1.023–54.996).Conclusions:Xba I gene polymorphisms in the ER α gene have correlation with MS and NMO. Xba I gene could be a risk factor of MS and NMO pathogenesis, especially the women with Xx genotype are more vulnerable. Xba I gene polymorphisms in the ER α gene may impact the disease duration of MS and NMO, or rather, the disease duration of Xx genotype persists longer than Xx genotype. Pvu II gene polymorphisms in the ER α gene has no correlation with MS and NMO.

Association of PRLR, IGF1, and LEP genes polymorphism with milk production and litter size in Egyptian Zaraibi goat

Studying variation in genes responsible for physiological characters is important to enhance goat productive and reproductive efficiency. This study aimed to detect specific nucleotide polymorphisms in prolactin receptor (PRLR), insulin-like growth factor (IGF1), and leptin (LEP) genes and their correlation with milk production (MP) and litter size (LS) traits in Zaraibi goat. PCR-SSCP products of different patterns of each gene were sequenced and aligned to reveal two mutations (T > C) and (G > A) in 3′UTR of PRLR gene and registered on NCBI with accession numbers OM418863 for TT and OM418864 for CT, while (G > A) variation was registered as OM418861 for GG and OM418862 for AG in exon 10. TT, CT, AG, and GG genotypes were distributed in the studied animals with frequencies 0.43, 0.57, 0.65, and 0.35, respectively. While alleles C, T, A, and G frequencies were 0.28, 0.72, 0.32, and 0.68, respectively. CT and AG genotypes associated significantly (P < 0.05) with higher MP and LS, respectively. By studying the haplotypes of PRLR, C-A and T-A were associated with the highest and the lowest level of MP, respectively. For LS, T-A and C-G showed significant correlation with the highest and the lowest rate, respectively. Regarding IGF1 gene, two polymorphisms were detected; T74C at exon 4 which registered on NCBI as OM418860, and combined mutations as ins. G470, A531G, and T534C (PP genotype) at 5′ flanking region that registered as OM418859. For LEP, only one polymorphism was found in intron 2 (G281A) which submitted to NCBI as OM418855. All detected polymorphisms have shown to be involved in regulating the MP or LS as reproductive traits in goat.

PIT 1 gene polymorphism and seasonality affect milk production traits in dairy cattle of Kashmir

The study aimed at identifying the best genotypes for important candidate PIT 1 gene and seasonality influencing the yield and quality of milk, in the Jersey and Crossbred HF cattle population maintained at an organized farm in Mountain Livestock Research Institute, Manasbal, Kashmir. The Jersey and Crossbred HF cows (60 each) were genotyped for quality and yield traits. Milk samples (50 ml) were collected on weekly basis for quality evaluation for the years 2016-18, among all the four seasons of Kashmir. The milk quality traits studied were fat%, lactose%, protein%, SNF, density and ash. The quantity traits were average monthly milk yield, protein yield and fat yield. Genomic DNA was extracted using Phenol-chloroform method and association analysis was done. The PIT 1 exon VI (451 bp) was screened for polymorphisms using PCR-RFLP using HinfI restriction enzyme, revealing two genotypes (Pp and pp) for both the breeds. Allele ‘p’ was most frequently present in Crossbred HF cows (0.95) and Jersey cows (0.82). The genotype Pp in crossbred HF cows and pp in Jersey cows showed higher values for yield traits in all four seasons under study. In crossbred HF cows, the effect of genotype Pp was significant on fat% and SNF. The genotype pp effect was significant on fat% in Jersey cows. Winter and autumn seasons had significant effect on fat% in both breeds under study. Based on the study, it was concluded that breed, season, and genotype of the PIT 1 gene are highly associated with the milk quality and yield in the dairy cattle of Kashmir. Genome wide association studies are recommended for better understanding the effects of all genes on milk quality and quantity.

P-371 The role of pharmacogenetics for individualized adjuvant therapy in patients with recurrent implantation failures

Abstract Study question In women with recurrent implantation failure (RIF), could we improve IVF/ICSI outcomes after administration of appropriate adjuvant therapies depending on patient's genetic profile?. Summary answer In RIF patients carrying polymorphisms detected in p53, IL-11 and VEGF genes, the addition of aspirin and intralipids administration appears to be beneficial. What is known already RIF is a distressing phenomenon of obscure etiology. Among the putative factors associated with this condition, we have immunological factors (the presence of antiphospholipid antibodies, certain cytokines or NK cells in maternal serum), genetic alterations in the parents or embryos, uterine abnormalities, or the presence of endometritis. Recently, certain genetic polymorphisms in genes involved in embryo implantation mechanisms at the endometrial (p53 and VEGF), immunological (IL-11 and Apo-E) and thrombotic levels (F5, F2 and MTHFR) have been identified. Study design, size, duration 104 IVF cycles (2017-2021), corresponding to ninety-eight patients, were included in this retrospective study. RIF was defined as the failure of achieving an on-going pregnancy after the transfer of at least three good-quality embryos. Exclusion criteria were abnormal karyotype or sperm FISH, uterine malformations, or positive antiphospholipid antibodies. During the index cycle, these patients received different adjuvant therapies; the following were analyzed: hydroxychloroquine, intrauterine hCG instillation, scratching, intralipids, corticosteroids, aspirin, and low molecular weight heparin. Participants/materials, setting, methods To carry out the genetic profile, different SNPs were analyzed in p53 (rs1042522), VEGF (rs1570360), IL-11 (rs11668344), Apo-E (rs429358 and rs7412), F5 (rs6025), F2 (rs199963) and MTHFR (rs1801133 and rs1801131) genes.Taqman® Life Technologies allelic discrimination real-time-PCR and TRP-PLUS kit were used for the detection of the different alleles. The following IVF outcome variables were considered: positive b-hCG, clinical (gestational sac) and on-going (10 week) pregnancy rate. SPSSv20.0 was used for statistical analysis. Main results and the role of chance Polymorphisms associated with a higher risk for RIF were PR and PP genotype for p53 gene, GG for VEGF, GG for IL-11, E4 isoform for Apo-E, GA and AA for F5, GA and AA F2, TT and CC for MTHFR gene. Accordingly, 64% of patients included in our study showed a high-risk genetic profile for RIF. Genotype variants for p53, IL-11 and VEGF were the most prevalent among this population. A multivariate binary logistic regression for possible confounding factors (maternal age, embryo quality, oocyte origin, number of embryos transferred, PGT-A and other adjuvants treatments) showed that those patients with PR/PP genotype for p53, GG for VEGF and GG for IL-11, obtained significantly higher positive b-hCG, clinical and on-going pregnancy rates when aspirin was administered compared to other genotypes (p &amp;lt; 0.05). Furthermore, patients with GG genotype for VEGF, also obtained a significant improvement in positive b-hCG and clinical pregnancy rates after intralipids administration (p &amp;lt; 0.05). None of the other adjuvant treatments employed showed significant differences regardless of the genetic profile. Limitations, reasons for caution The inherent limitations of a retrospective analysis of a limited sample size. Wider implications of the findings IVF/ICSI outcome of RIF patients was analyzed according to the adjuvant treatment received and considering their genetic profile. Pharmacogenetics seems promising in identifying patients at high risk for RIF and may add in the optimization of specific pharmacotherapy depending on the genetic background of each infertile woman. Trial registration number not applicable

LincRNA#1 knockout alone does not affect polled phenotype in cattle heterozygous for the celtic POLLED allele

A long intergenic non-coding RNA (lincRNA#1) is overexpressed in the horn bud region of polled (hornless) bovine fetuses, suggesting a potential role in horn bud suppression. Genome editing was used to test whether the absence of this sequence was associated with the horned phenotype. Two gRNAs with high mutation efficiencies targeting the 5′ and the 3′ regions flanking the lincRNA#1 sequence were co-injected with Cas9 as ribonucleoprotein complexes into bovine zygotes (n = 121) 6 h post insemination. Of the resulting blastocysts (n = 31), 84% had the expected 3.7 kb deletion; of these embryos with the 3.7 kb deletions, 88% were biallelic knockouts. Thirty-nine presumptive edited 7-day blastocysts were transferred to 13 synchronized recipient cows resulting in ten pregnancies, five with embryos heterozygous for the dominant PCPOLLED allele at the POLLED locus, and five with the recessive pp genotype. Eight (80%) of the resulting fetuses were biallelic lincRNA#1 knockouts, with the remaining two being mosaic. RT-qPCR analysis was used to confirm the absence of lincRNA#1 expression in knockout fetuses. Phenotypic and histological analysis of the genotypically (PCp) POLLED, lincRNA#1 knockout fetuses revealed similar morphology to non-edited, control polled fetuses, indicating the absence of lincRNA#1 alone does not result in a horned phenotype.

Genetic associations of TP53 codon Pro72Arg polymorphism (rs1042522) in coronary artery disease: A meta-analysis of candidate genetic mutants

BackgroundThe tumour suppressor p53 gene involved in cell cycle regulation and exhibit important role in atherosclerosis. Both genetic and environmental risk factors play an important role and confer susceptibility to coronary artery disease (CAD). A functional polymorphism Pro72Arg located on codon 72 (rs1042522) at exon 4 may influence CAD pathophysiology. MethodsCorrelate the association of TP53 gene with CAD by increasing various statistical parameters, a meta-analysis of 7 studies were performed. ResultsA significant correlation between Pro72Arg polymorphisms and reduced CAD risk observed in Caucasian subgroup. In recessive comparison model a significant reduced CAD risk was found in pooled out data (PP vs PP + RP: odd ratio (OR) = 0.338, 95% confidence interval (CI) = 0.238 to 0.47, P = 0.00*) and also in Caucasian subgroup (PP vs PP + RP: OR = 0.296, 95% CI = 0.185 to 0.473, P = 0.00*), (PP vs PP + RP: OR = 0.326, 95% CI = 0.193 to 0.552, P = 0.00*), (PP vs PP + RP: OR = 0.140, 95% CI = 0.076 to 0.258, P = 0.00*), (PP vs PP + RP: OR = 0.269, 95% CI = 0.138 to 0.525, P = 0.00*), Black subgroup (PP vs PP + RP: OR = 0.386, 95% CI = 0.226 to 0.657, P = 0.00*) and Asian subgroup (PP vs PP + RP: OR = 0.467, 95% CI = 0.284 to 0.767, P = 0.00*). ConclusionsPresent meta-analysis suggest that PP genotype of the p53 Pro72Arg polymorphism reduces the risk of CAD significantly in Caucasian population. However, the future studies considering the gene-environment interaction are needed to confirm the observed association.

Measurement of the Gene Expression and Polymorphisms of c-myc and p53 Genes in HBV Infected Patients

This study explained the c-myc and p53 gene expression and polymorphisms in chronic (40), cirrhosis (30) and Hepatocellular Carcinoma, (HCC) (30) patients related to Hepatitis B Virus (HBV) infection and healthy control (50) in Egypt. Where, c-myc (intron 8) and p53 (codon 72) gene expression and polymorphisms were determined using qRT-PCR and PCR-RFLP techniques. The results showed that c-myc gene expression (2-ddct) was significantly increased in chronic (1.38), cirrhosis (1.47) and HCC (5.59) compared to the control group (1.00), while p53 gene expression (2-ddct) was significantly decreased compared to the control group (0.82, 0.65, 0.33 and 1.00, respectively). In HCC group, c-myc genotype (CC) was predominant (90%) more than cirrhosis, chronic and control (73.33, 22.5 and 6%, respectively), GG genotype was predominant in control (70%) more than chronic, cirrhosis and HCC groups (67.5, 6.66 and 6.66%, respectively) and GC genotype was high in control (24%) more than cirrhosis, chronic and HCC groups (20, 10 and 3.33%, respectively). p53 PP (88%) genotype was predominant in control more than chronic, cirrhosis and HCC groups (30, 30 and 6.66%, respectively), AA genotype was predominant in HCC group (73.33%) more than chronic, cirrhosis and control (50, 10 and 4%, respectively) and genotype PA was predominant in cirrhosis (60%) more than chronic, HCC and control (20, 20 and 8%, respectively). These results suggest clearly that both c-myc and p53 gene expression and polymorphisms influence clinical outcome and progression of HBV infection and then considered an accurate genetic biomarker to determine and predict the progression of HBV infection.

Estrogen receptor α polymorphism is associated with dementia in a Brazilian cohort.

The growth of the elderly population is a worldwide phenomenon and it is associated with chronic diseases, including dementia. In this scenario, the present study aimed to evaluate a possible association of estrogen receptor α polymorphisms with dementia in a Brazilian cohort. The subject sample was divided into two groups, control (n = 105) and case (n = 73), according to analysis of two predictive dementia tests (MMSE and CDR). The genotyping for the ERα PvuII (c.454-397T>C, rs2234693) and XbaI (c.454-351A>G, rs9340799) polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. The ERα PvuII pp genotype was associated with higher odds ratio for dementia (OR = 3.42, 95% CI = 1.33–8.77, p = 0.01, in a model including covariates. A linear regression model identified significant associations of the ERα PvuII genotypes (independent variable) with CDR scale (dependent variable), β = 0.26 and p = 0.001. In conclusion, estrogen receptor α PvuII polymorphism is associated with dementia in a Brazilian cohort. This finding may be useful for the identification of a possible set of significant genetic and clinical biomarkers for better understanding pathophysiology, early diagnosis and management of dementia.

ESTROGEN RECEPTOR 1 POLYMORPHISMS (PVUII AND XBAI) AND TEMPOROMANDIBULAR JOINT INTERNAL DERANGEMENT SUSCEPTIBILITY IN A GROUP OF TURKISH PATIENTS

Ponte Academic JournalFeb 2020, Volume 76, Issue 2 ESTROGEN RECEPTOR 1 POLYMORPHISMS (PVUII AND XBAI) AND TEMPOROMANDIBULAR JOINT INTERNAL DERANGEMENT SUSCEPTIBILITY IN A GROUP OF TURKISH PATIENTSAuthor(s): Ayca Dilara YILMAZJ. Ponte - Feb 2020 - Volume 76 - Issue 2 doi: 10.21506/j.ponte.2020.2.16 Abstract:Aims: Temporomandibular joint internal derangement (TMJ-ID) is the impairment of the metabolic processes in the extracellular matrix of the articular disc causing progressive tissue breakdown. Objective: The aim of this study was to investigate the association of XbaI and PvuII polymorphisms with TMJ-ID and to evaluate susceptibility to the disorder. Methods: Unrelated TMJ-ID patients (age= 31.7±7.9) (n=48; 38 female, 10 male) and healthy controls (age=28.22 ± 5.9) (n=70; 33 female, 37 male) were included in the study. DNA extraction was done by standard proteinase K/phenol-chloroform method. Polymorphisms of the Estrogen receptor 1 gene (ESR1) was investigated by a polymerase chain reaction based restriction fragment length polymorphism assay. Results: TMJ-ID patients, and the subgroups; TMJ-ID anterior disc displacement with reduction (ADDwR) and TMJ-ID anterior disc displacement without reduction (ADDwoR) cases carrying the Pp and pp genotype had a 1.28/1.27, 1.43/1.90 and 1.18/0.81-fold odds ratio (p>0.05), respectively. ESR1 polymorphisms revealed five different genotypes in both the patient and the control groups; PXpx (45.6%/47.05%), PXPX (21.7%/27.9%), pxpx (13.04%/13.2%), PXpX (15.2%/8.83%) and PXPx (4.3%/2.94%). The pxpx genotype had a 2.30 fold odds ratio in women. Conclusion: The results from this study did not confirm susceptibility of VDR polymorphisms to TMJ-ID, however, these variations should be further evaluated in a larger cohort study. Keywords: Temporomandibular joint internal derangement, temporomandibular joint osteoarthritis, anterior disc displacement with reduction, anterior disc displacement without reduction, ERα, ESR1 Download full text:Check if you have access through your login credentials or your institution Username Password

Association of GPx1 P198L and CAT C-262T Genetic Variations With Polycystic Ovary Syndrome in Chinese Women.

Background: Oxidative stress plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Glutathione peroxidase 1 (GPx1) and catalase (CAT) are the major intracellular antioxidant enzymes that can detoxify hydrogen peroxide into water, preventing cellular injury from reactive oxygen species. The aim of the present study was to investigate the association of GPx1 P198L (Pro198Leu, C559T, rs1050450) and CAT C-262T (rs1001179) genetic polymorphisms with the risk of PCOS and evaluate the effects of the genotypes on clinical, hormonal, metabolic and oxidative stress parameters in Chinese women.Methods: This is a case-control study of 654 patients with PCOS and 535 controls. The GPx1 P198L, CAT C-262T, and superoxide dismutase 2 (SOD2) A16V genotypes were determined by polymerase chain reaction amplification and restriction analysis. Clinical, hormonal, metabolic and oxidative stress parameters were also analyzed.Results: The frequencies of the PL + LL genotype (14.1 vs. 8.4%) and L allele (7.3 vs. 4.4%) of GPx1 P198L polymorphism were significantly higher in patients with PCOS than in control subjects. Genotype (PL + LL) remained a significant predictor for PCOS in prognostic models including age, body mass index (BMI), insulin resistance index, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as covariates (OR = 2.105, 95%CI: 1.330–3.331, P = 0.001). Patients carrying the L allele had relatively high average ovarian volume, waist circumference, and malondialdehyde levels (P < 0.07) compared with patients with the PP genotype. We also demonstrated that the subjects with both GPx1 L and SOD2 A alleles further increase the risk of PCOS compared with the individuals carrying the PP/VV genotype after adjusting for age and BMI (OR = 5.774, 95%CI: 2.243–14.863, P < 0.001). However, no significant differences were observed in the frequencies of the CAT C-262T genotypes and alleles between PCOS and control groups.Conclusions: The GPx1 P198L, but not CAT C-262T, genetic polymorphism is associated with the risk of PCOS in Chinese women.

Association of COL1A2 (PvuII) gene polymorphism with risk and severity of dental fluorosis – A case control study

IntroductionDental fluorosis is a foremost public health problem in many countries, including India. Very few studies investigated gene polymorphism and risk of dental fluorosis. Genetic polymorphisms in Collagen Type I, alpha 2 (COL1A2) gene, found to be linked with bone pathogenesis, may affect the tooth formation resulting in the vulnerability to dental fluorosis. AimTo assess the association between COL1A2 (PvuII) gene polymorphism and risk as well as severity of dental fluorosis. MethodsThe present case control study was conducted among participants with (n = 60) and without (n = 60) dental fluorosis. Dental fluorosis was assessed using Modified Dean’s fluorosis index (1942). The PvuII polymorphisms (in exon 25) inside the COL1A2 gene were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure. Statistical analysis were carried out with Chi-square test and Odds Ratio (OR) was determined with multivariate logistic regression analysis. ResultsThe genetic polymorphism in COL1A2 PvuII was found to be associated with the risk of dental fluorosis which was highly significant (p < 0.001). The odds ratio was 31.4 times [OR = 31.9, 95% CI: 3.9–48.7] higher for the homozygous PP genotype group and 4.0 times [OR = 4.0, 95% CI: 1.0–10.7] higher for the heterozygous Pp genotype. ConclusionGenetic polymorphism of COL1A2 was found to be associated with dental fluorosis. The present study provides an insight for identification of the population who may subsist at risk of developing dental fluorosis in their later life.

Strategies and cost–benefit of selecting for a polled sheep nucleus by using DNA testing

The present study assessed the effectiveness and cost–benefit of several genotyping strategies for breeding poll Merino sheep in a closed nucleus with different initial allele frequencies and assuming a single-gene responsible for the horn or poll phenotype. We assumed that selection was based on phenotypes or genotypes for a single gene conferring polledness via a complete-dominance model. Under such a model, a complete fixation of the ‘polled allele’ (P) requires genotyping of the ewe-selection candidates. Testing a higher proportion of female candidates resulted in a faster fixation of the P-allele. Fixation ranged from 1 year of selection with a high starting P-allele frequency of 0.9, to 7 years for low starting P-allele frequencies of 0.3. When premiums of AU$50 or AU$100 were paid for rams with a PP genotype, breeding for PP genotypes was not profitable when the starting P-allele frequency was below 0.7. If the starting allele frequency was above 0.7, net profitability was positive over 10 years when premiums of AU$200 were paid for known PP-genotype rams. While fixing the P-allele, genetic gain for production traits was slowed down in the first 5 years of selection by up to 23% and 3% for initial P allele-frequencies of 0.3 and 0.9 respectively. Lost genetic gain due to fixing the P-allele, which can never be recovered in a closed nucleus, incurred 200–800% higher costs than the DNA testing costs. Rates of genetic gain recovered to pre-P-allele selection level rates of genetic gain once the P-allele was fixed. Testing a maximum of 25% ewe-selection candidates was the least expensive strategy across all starting allele frequencies and premiums. To avoid large losses of genetic gain in a closed nucleus with low P-allele starting frequencies, opening the nucleus should be considered to increase starting P-allele frequencies and also to potentially increase rates of genetic gain to offset the economic loss caused by P-selection.

Impact of occupational cadmium exposure on bone in sewage workers.

Cadmium (Cd) is one of the environmental risk factors for bone loss. The present study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed men were included as a control group. Current smokers represented 65% and 47.5% of the exposed and control groups, respectively. The study aimed to investigate the hazard of occupational Cd exposure on bone health. This was achieved through measuring serum and urinary Cd, and calcium (Ca), in addition to serum osteoprotegerin (OPG) and estrogen receptor-α gene. Results showed significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed compared to the controls. Bony aches and joint pain were more prevalent among the exposed workers. Serum and urinary Cd increased in exposed smokers relative to control smokers. Also, serum OPG levels showed significant rise among exposed smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd level increased significantly in PP and pp genotypes in exposed workers compared to controls, while elevated levels of serum OPG was observed in PP and Pp genotypes in exposed workers relative to controls. Urinary Cd exhibited significant rise in both PP and pp genotypes in exposed workers, while Ca excretion was elevated in pp genotype only. The study reflected an association of genetic predisposition and Cd exposure in progression of osteoporosis. Further research is needed to explain the mechanisms of Cd impact on bone. The role of smoking is important and hence smoking cessation programs are essential for sewage workers.

Associations between ER\u03b1/\u03b2 gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis

BackgroundMany studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERβ gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.MethodsPubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association.ResultsOverall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERβ RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations.ConclusionEach ERα and ERβ gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.

TP53 polymorphism in plasma cell myeloma.

Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients. Genomic DNA from newly diagnosed 59 patients (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of 40 PCM patients were treated with bortezomib (1, 2 and 4 nM). The P allele of the P72R polymorphism was more common than the R allele in PMC patients compared to controls (39% vs. 24%), and the difference was significant (p = 0.02). The PP and PR genotypes (in combina-tion) were more frequent among cases than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level and 2 nM bortezomib concentration the PP genotype was associated with higher necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed in patients with the PP genotype compared to patients with the PR or RR genotypes (20 months) (p = 0.04). The results suggest that P72R polymorphisms may be associated with an increased PCM risk and may affect OS of PCM patients. However, we saw no consistent results of the polymorphism effect on apoptosis and necrosis in cell cultures derived from PCM patients. Further studies are need in this regard.

Effect of the Pro12Ala Polymorphism of the Peroxisome Proliferator-activated Receptor γ2 Gene on Lipid Profile and Adipokines Levels in Obese Subjects.

Peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of metabolism, adipokines production and secretion. The aim of this study was to investigate the association between the PPARγ2 gene Pro12Ala polymorphism in obesity in terms of body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), serum lipid, leptin, adiponectin, resistin and chemerin levels. The study included 160 obese and 140 non obese subjects. The Pro12Ala polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid, leptin, adiponectin, resistin and chemerin levels were measured. No association was found between the Pro12Ala polymorphism and BMI. Strikingly, in the study group, obese subjects with the AA genotype had significantly higher triglycerides (p = 0.046) and resistin (p <0.001) levels than those with the wild-type PP and heterozygous PA genotypes. Serum leptin and chemerin levels were significantly associated with Pro-12Ala poymorphism in the obese and non obese groups (p <0.01). In the obese group, subjects with the homozygous AA genotype had significantly lower adiponectin (p = 0.010) activity than the PP genotype. Our results suggest that the PPARγ2 gene Pro12Ala polymorphism has no direct association with obesity but does have significant influences on lipid profiles and adipokines levels.

Association of C-myc and p53 Gene Expression and Polymorphisms with Hepatitis C (HCV) Chronic Infection, Cirrhosis and Hepatocellular Carcinoma (HCC) Stages in Egypt

The aim of this study is to investigate c-myc and p53 gene expression and polymorphisms in different stages of HCV infection,. Expression levels of c-myc and p53 were evaluated by RT-PCR and polymorphisms were determined by PCR-RFLP in 60 HCV patients classified into chronic infection, cirrhosis and HCC groups along with 30 controls. c-myc gene expression significant increased through the stages as compared to the control level (1.17, 1.82, 3.33 and 0.32, respectively), whereas p53 significantly declined (4,375, 3,842, 525 and 5,498, respectively). The C-myc CC genotype was predominant in the HCC group (90%) to a greater extent than in the cirrhosis, chronic infection and control cases (80%, 20% and 10%, respectively), while the GG genotype was predominant in controls (83%, as compared to 65%, 10% and 10%). The CG genotype was most common in chronic infection (15%). The p53 PP genotype predominated in controls (87%, with 15%, 10% and 20%, respectively, for the three stages) while the AA genotype demonstrated only slight increase to HCC (13%, 25% and 30%, respectively) and PA genotype was predominant in cirrhosis cases (90%). These findings reveal that c-myc and p53 gene expression and polymorphisms may be considered as promising sensitive genetic biomarkers for progression of HCV infection.

Association of TAS2R38 variants with sweet food intake in children aged 1–6 years

We aimed at studying whether genetic variants of the TAS2R38 gene are associated with energy intake from sweet tasting foods, total energy and macronutrient intake and body weight in children.Children (n = 691) from five European countries were genotyped for the first variant site rs713598 of the TAS2R38 bitter receptor gene. Three-day dietary records were obtained yearly from one to six years of age. Foods were categorized in sweet and non-sweet-tasting. Mixed models were used to describe group differences in food and nutrient intake and BMI z-score over time.TAS2R38 genotype was related to energy intake from sweet tasting foods: Children with PP and PA genotype consumed an average 83 kJ/d (95% CI 21 to 146; p = 0.009) more sweet tasting foods than children with AA genotype and a mean 56 kJ/d (95% CI 15 to 98; p = 0.007) more energy from energy dense sweet products. Intake of sweet tasting foods was lower in girls than boys and differed between countries. TAS2R38 genotype was not associated with the intake of energy, macronutrients, sugar, single food groups and BMI z-score.Despite many other factors influencing food preference and intake in children, actual intake of sweet food items is associated with TAS2R38 genotype. Children with PP or PA genotype consume more (energy dense) sweet tasting foods.

Endemic fluorosis in Henan province, China: ERα gene polymorphisms and reproductive hormones among women.

The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence. A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride. In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05). Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.

Genetic predisposition of variants in TLR2 and its co-receptors to severe malaria in Odisha, India.

Although the role of TLRs signalling in malaria pathogenesis is well established, contribution of individual TLR to clinical outcome of malaria still remains inconclusive. Given the importance of TLR2 and its co-receptors in recognising distinct structural forms of key malaria toxins and mediating innate immune response, it is essential to delineate their genetic contribution. Variants in TLR1 (I602S) and TLR6 (P249S) were genotyped by PCR-RFLP methods, and TLR2 (I/D) was genotyped by PCR in 200 samples each from uncomplicated malaria (UM) and severe malaria (SM). Further, SM was categorised into its sub-clinical groups (CM and NCSM or SOD and MODS) and analysed. The results showed the PP genotype of TLR6 (P249S) to be significantly more common in UM (P < 0.0001), whereas the 'SS' genotype was the risk factor for SM including its sub-clinical categories. The TLR1 (602S) and TLR2 (D) variants were significantly high in patients with CM; however, negative LD was observed between TLR2 and TLR6 in NCSM and MODS. Haplotype analysis showed significantly high frequency of I-I-S haplotype in all forms of subclinical SM and was associated with low parasite load in SM (P = 0.013). The haplotypes I-D-S and S-I-P were significantly high in SOD and CM, respectively. The TLR6 '249S' variant appeared to be the dominant determinant for genetic predisposition to SM and that its association with either TLR2 'D' or TLR1 '602S' modulates for CM development. The present study opens up several new avenues for their exploration and validation in future studies in different global settings for malaria.