DD Genotype Research Articles

Association of caspase 8 promoter variants and haplotypes with the risk of breast cancer and its molecular profile in an Iranian population: A case‐control study

Caspase 8 (CASP8) gene plays a key role in the regulationof apoptotic cell death. Expression variation in this gene has been associated with the risk of breast cancer. The aim of this study was to investigate the association of rs3834129 and rs3769821, as functional variants, and their haplotypes with molecular profile as well as the risk of breast cancer in an Iranian population. A case-control study was conducted on 812 participants including 293 breast cancer patients and 519 healthy controls. Genotyping was performed by polymerase chain reaction-based methods. Statistical analysis was performed using SPSS Ver16. The association between polymorphisms and haplotypes with the risk of breast cancer was estimated by calculating odds ratios (OR) and chi-square (χ2 ) tests. In comparison with ins allele (I) of rs3834129, carriers of del allele (D) showed a lower risk of breast cancer (OR, 0.65; 95% confidence interval [CI], 0.49-0.87; P = 0.004). The multivariate logistic regression model indicated DD genotype as an independent factor for a decreased risk of breast cancer in our population (OR, 0.18; 95% CI, 0.06-0.58; P = 0.004). Also, the C allele of rs3769821 was associated with a 43% increased risk of breast cancer (P = 0.005); however, after adjustment for confounding factors, no association with rs3769821 and breast cancer was observed. In addition, D-T haplotype and diplotype presented protective effects (P < 0.05). Our results indicate that genetic variations in the promoter region of CASP8 gene, especially rs3834129, may serve as a genetic risk factor for breast cancer in an Iranian population.

Role of ACE I/D polymorphism in pathological assessment of preeclampsia in Pakistan.

BackgroundPreeclampsia (PE) is a pregnancy‐related hypertensive disorder, which may stem from impair placentation. Renin‐angiotensin system is one of the mediators of decidualization and trophoblastic proliferation. In the present study women with PE were studied in a comparison of normotensive controls to determine whether Angiotensin‐converting enzyme (ACE) gene I/D polymorphism affect the placental villi and umbilical cord formation with the assessment of biochemical and clinical risk factors.MethodsTotal 400 blood (PE/controls = 200), 400 urine (PE/controls = 200), 90 tissue samples of UC (PE = 50, controls = 40) and 90 placental tissue samples (PE = 50, controls = 40) were recruited. Histomorphological and Histomorphometric analysis were done for placental and umbilical cord tissues. Blood and serum parameters were analyzed, samples were genotyped for I/D polymorphism. Data were statistically analyzed by Independent sample t‐test, Chi‐square test and the odds ratio.ResultsHistological study revealed significant increase (p < 0.001) in distance from Wharton jelly (in both artery and vein) and outer layer thickness of vein; significant reduction (p < 0.01 and p < 0.05) in the lumen area of artery and vein. Abnormal villi, more syncytial knots (SK) and a significant decrease in elongated and large villi in PE placentas. Analysis of ACE gene determined that genotypic frequencies were statistically significant (p < 0.02) among both groups and DD genotype was predominant in the PE group.ConclusionPresent study reveals that ACE I/D polymorphism might affect the normal placental villi and umbilical cord formation in women with PE. In addition, histological studies and genetic evaluation can provide useful information in the determination of various reasons and mechanisms involved in the pathogenesis of PE in Pakistan.

A meta-analysis on the association of genetic polymorphism of the angiotensin-converting enzyme and coronary artery disease in the chinese population.

To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.

Assessment of meat quality defect genes in indigenous pigs of Bareilly region.

This investigation was undertaken to assess the population of indigenous (Bareilly local) pigs for meat quality genes (RYR1, PRKAG3, HFABP, MYF-5, and MC4R). The results showed that indigenous pigs were monomorphic at RYR1locus (100% NN genotype), HFABP locus (100% HH genotype), and MYF-5 locus (100% DD genotype). Homozygote RR and heterozygote QR genotypes were observed at PRKAG3 (c.599 G>A) SNP locus with 89 and 11% frequency. The frequency of wild (R) and mutant (Q) allele at the said locus was 95 and 5%. The MC4R SNP had three genotypes; homozygote AA with 5% frequency, heterozygote AG with 53% frequency, and homozygote GG with 42% frequency. Corresponding frequency of A and G allele was 32 and 68%, respectively. Monomorphic status at RYR1locus for NN genotype, HFABP locus for HH genotype, and MYF-5 locus for DD genotype indicated that favorable genes for quality pork production have been fixed in the population. The higher frequency of RR genotype (89%) at PRKAG3 and GG genotype (42%) at MC4R locus further explained the existence of favorable genotypes in indigenous pigs.

Effects of 8 weeks of moderate-intensity resistance training on muscle changes in postmenopausal women with different angiotensin-converting enzyme insertion/deletion polymorphisms of interest

The aim of the study was to explore the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and muscle adaptations to moderate-intensity resistance training in postmenopausal women. Forty healthy postmenopausal Chinese women (aged 53-66 years) were recruited and grouped by ACE I/D polymorphism (the homozygous deletion genotype [DD], n = 12; the I allele carriers [II/ID], n = 28). All participants performed an 8-week full-body resistance training program at moderate intensity with 15-repetition maximum. Upper- and lower-limb muscle mass, grip and back strength, anatomical cross-sectional area of the rectus femoris (ACSARF), isokinetic knee extension strength (MVCKE) and knee flexion strength were measured before and after training. Our results showed significant genotype × time interaction in ACSARF and MVCKE (P = 0.007 and P = 0.03, respectively) with the DD group having greater changes in corresponding parameters than the I-allele carriers (P = 0.012 and P = 0.018, respectively). Multivariate linear regression results showed that the ACE DD genotype was positively related to the grip strength adaptation (r = 0.48, P = 0.05). This study improves our understanding of the association between the ACE I/D polymorphism and muscular responses to moderate intensity resistance training among postmenopausal women and revealed that the DD genotype has predominant adaptations in grip strength, rectus femoris size, and knee extensor strength.

Deletion Polymorphism of Angiotensin Converting Enzyme Gene is Associated with Left Ventricular Hypertrophy in Uighur Hypertension-Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) Patients.

BackgroundThis study aimed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphisms with left ventricular hypertrophy (LVH) in Han and Uighur hypertension-OSAHS (obstructive sleep apnea hypopnea syndrome) patients in China.Material/MethodsA total of 162 Han and 72 Uygur patients with hypertension-OSAHS were independently subdivided into an LVH group and a non-LVH (NLVH) group based on the left ventricular mass index. The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction. The association of ACE gene insertion/deletion polymorphisms with LVH was assessed by chi-squared test. Logistic regression analysis was performed to obtain the odds ratios and 95% confidence intervals for the risk of LVH after adjusting for confounding factors.ResultsIn Uighur patients, the distributions of D allele and DD genotype showed significant differences between the LVH group and the NLVH group. The difference of DD genotype remained significant after multivariate adjustment. In contrast, no significant differences were observed in the distributions of D allele and DD genotype between the LVH group and the NLVH group in Han patients. Moreover, moderate-severe OSAHS was an independent risk factor for LVH.ConclusionsD allele and DD genotype of ACE gene are possible genetic markers for the risk of LVH in Uighur but not Han hypertension-OSAHS patients.

Analysis of the Association Between Polymorphisms within PAI-1 and ACE genes and Ischemic Stroke Outcome After rt-PA Therapy.

Treatment of Ischemic stroke (IS) in acute phase is based on the use of thrombolytic rt-PA therapy. We aimed to determine whether different alleles and genotypes of I/D ACE gene and 4G/5G PAI-1 gene polymorphisms may influence outcome of rt-PA therapy in patients with IS and the occurrence of haemorrhagic transformation (HT). Our study included 94 consecutive patients with IS treated with rt-PA. Modified Rankin Scale (mRS) at 3rd month after IS was used to determine the stroke outcome, with scores 0-1 defining the favourable outcome, and scores 2-6 defining poor outcome. Genotypisation of the ACE-1 I/D polymorphism was performed by polymerase chain reaction and of the PAI-1 4G/5G polymorphism by polymerase chain reaction - restriction fragment length analysis. Regarding PAI-I 4G/5G polymorphism, 44 patients (46.8%) were heterozygotes, and the number of 4G/4G and 5G/5G homozygotes was the same - 25 each (26.6%). Number of heterozygotes for the ACE I/D polymorphism was 54 (57.4%), 9 patients (9.6%) had II, and 31 (33%) DD genotypes. A favourable outcome was recorded in 26 (28.0%) and the poor outcome in 67 (72.0%) patients. Favourable and poor outcome groups did not differ significantly in PAI-1 4G/5G and ACE I/D polymorphisms genotype or allele frequencies. There was a statistically significant difference in the occurrence of HT between patients with ACE II and patients with ACE ID or DD genotypes (p=0.035). Results of our study suggest that stroke patients with ACE II genotype, treated with rt-PA, may be at risk of HT.

NFKB1 gene rs28362491 polymorphism is associated with the susceptibility of acute coronary syndrome.

The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. NF-κB, a central regulator of inflammation, is involved in various inflammatory diseases. The aim of the present study was to explore the association between NFKB1 gene rs28362491 (-94ATTGins/del) polymorphism and ACS. A total of 778 ACS patients and 1112 healthy subjects were included in our study. The TaqMan SNP genotyping assays was used to analyze the rs28362491 polymorphism. The lesion extent of coronary artery was assessed by Gensini Score and lesion vessel number in ACS patients. For total and males, the frequencies of the mutant DD genotype and D allele were significantly higher in ACS patients than that in control subjects (total: DD genotype: 18.0 vs 14.1%, P=0.009, D allele: 43.0 vs 37.9%, P=0.002, males: DD genotype: 20.6 vs 15.3%, P=0.042, D allele: 44.2 vs 38.8%, P=0.013). After multivariate logistic regression analysis, we found that individuals with mutant DD genotype had 1.329-fold higher risk of ACS compared with individuals with ID and II genotypes. Moreover, ACS patients with DD genotype were worse stenosis of coronary artery compared with patients carrying II or ID genotype. In conclusion, our study demonstrated that the mutant DD genotype of NFKB1 gene was associated with the risk and severity of ACS in Han population in Xinjiang, northwest of China.

Two indel variants of prolactin receptor (PRLR) gene are associated with growth traits in goat

Prolactin receptor (PRLR) gene plays a crucial role in the milk production, reproduction and the growth of mammals. To fully characterize the structure of the mutation and to further study the function of the goat PRLR gene, two insertion/deletion (indel) loci (12 bp; 16-bp; 5-bp) were detected in 1038 Shaanbei white cashmere (SBWC) goats. Associated analysis revealed that the 16-bp indel mutation was significantly associated the body length, body height, chest depth (CD), body length index (BLI), heart girth index and cannon circumference index (CCI) (p < 0.05). The polymorphism of 5-bp indel was significantly associated with CD, heart girth, CCI and BLI (p < 0.05). Overall, individuals with genotype DD showed better phenotypic traits than individuals with other genotypes at the two loci of PRLR gene in SBWC goat. These findings suggested that the two novel indels within the caprine PRLR gene could be considered as effective DNA molecular markers and could provide a valuable theoretical basis for the application of marker-assisted selection in the goat industry.

РОЛЬ ПОЛИМОРФИЗМОВ ГЕНОВ ГАМКЕРГИЧЕСКОЙ СИСТЕМЫ В ФОРМИРОВАНИИ СИНДРОМА ОБСТРУКТИВНОГО АПНОЭ СНА У БОЛЬНЫХ БРОНХАЛЬНОЙ АСТМОЙ

The results of recent studies indicate the potential role of gamma-aminobutyric acid (GABA), as an inhibitory mediator of the central nervous system, in the pathogenesis of obstructive sleep apnea syndrome (OSAS) ‒ a common disorder that often accompanies asthma. The aim of the study was to investigate the possible role of some GABAergic system genetic polymorphisms in the formation of OSAS in asthma patients. Overnight cardiorespiratory monitoring was performed to diagnose OSAS and spirometry was conducted to evaluate the airway reactivity to the bronchodilator fenoterol in 184 asthma patients. Polymorphisms of GAD1, GAD2, GABBR1 and GABBR2 genes (15 polymorphisms in total) were genotyped by LATE-PCR method. Significant results were obtained for rs3749034 polymorphism of GAD1 gene and rs35400353 of GABBR2 in association analysis with the presence of OSAS. rs3749034 significantly influenced the presence of OSAS in males, which was accompanied by the predominance of the CC genotype among patients with OSAS, while CT+TT genotypes were more common in patients without OSAS (OR 3.9 95%CI [1.36–11.67], p=0.01). In total sample GAD1 rs3749034 polymorphism was an independent factor increasing the likelihood of having OSAS after adjustment for significant confounders (OR 1.9 95%CI [1.23–3.15], p=0.005). rs35400353 polymorphism was also associated with OSAS after adjustment for confounders, although its relationship was less significant (OR 1.5 95%CI [1.1–2.3], p=0.04). There was a tendency for interrelation with airway hyperresponsiveness to bronchodilator for both polymorphisms: rs3749034 ‒ in case of CT+TT genotypes, rs35400353 ‒ in case of DD genotype. rs3749034 polymorphism also significantly influenced lung function parameters. After additional verification of the results, the identified genetic polymorphisms may be used to individually predict the risk of OSAS as well as for the development of personalized approaches in asthma treatment using GABA.

Association of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with the Risk of Atherosclerosis

Aims: The objective of this study was to perform a meta-analysis to evaluate the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to atherosclerosis (AS). Methods: MEDLINE, EMBASE, and the ISI Web of Science were searched for all eligible published studies concerning the relationship of ACE gene polymorphism with AS without language restrictions. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate this relationship under different genetic models using meta-analytic methods. Results: A total of 15 articles (16 studies) were involved in this meta-analysis. The D allele of the ACE gene had a nonsignificant increase in the risk of AS (D versus I: OR = 1.23, 95% CI, .98-1.53, P = .07; I2 = 87.2%, Pheterogeneity < .01). Compared with the II genotype, the DI (relative risk [RR]: 1.35, 95% CI: 1.09, 1.67, P < .01; I2 = 47.8%, Pheterogeneity = .017) and (DD + DI) (RR = 1.38, 95% CI: 1.04, 1.82, P = .02; I2 = 73.3%, Pheterogeneity < .01) genotype of ACE was associated with higher risk of AS, respectively. Subjects with the DD genotype showed a statistically nonsignificant trend toward greater risk of AS (RR = 1.53, 95% CI: .97, 2.43, P = .07; I2 = 88.6%, Pheterogeneity < .01). Further subgroup analyses showed that significant relationships were only found in Europeans under different gene polymorphism or different genotype models rather than Asians. Conclusions: The present meta-analysis indicated that the D allele in the ACE gene was associated with the risk of AS, especially in Europeans. Furthermore, increased copy number of D allele was significantly associated with increased AS risk in a dose-dependent manner.

Association between ACE gene I/D polymorphism and knee osteoarthritis in a Chinese population.

Osteoarthritis (OA) is a degenerative joint disease characterized by joint destruction with cartilage loss and occasional gross derangement of joint integrity. In recent years, several studies have reported the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and knee OA. However, the results were conflicting. To determine the association between ACE gene I/D polymorphism and knee OA, we conducted a hospital-based case–control study with 282 knee OA cases and 316 controls to investigate the association between ACE gene I/D polymorphism and knee OA susceptibility in a Chinese Han population. The present study found that DD genotype or D allele carriers of ACE gene I/D polymorphism increased the risk of knee OA. Stratification analyses of sex, age, and body mass index (BMI) showed significant associations amongst the groups of females, ≥55 years, and abnormal BMI. In addition, the present study made analysis between ACE I/D polymorphism and some clinical features of OA, and found DD genotype of I/D polymorphism was associated with arthralgia. Furthermore, we undertook a meta-analysis together with the present study between this single nucleotide polymorphism (SNP) and knee OA risk. This meta-analysis found that ACE gene I/D polymorphism was associated with increased risk for OA. Stratification analysis of ethnicity in this meta-analysis indicated that I/D polymorphism increased the risk of knee OA amongst the Asians and Caucasians. In conclusion, this case–control study and meta-analysis suggest that ACE gene I/D polymorphism is associated with increased risk for knee OA.

Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients withBC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

Screening of Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme gene.

Background/aims: The role of angiotensin-converting enzyme (ACE) gene polymorphism in the development of obesity and hypertension in children has not been widely studied. We aimed to screen Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in the ACE gene.MethodsOne hundred forty-two children and adolescents were included (70 with simple obesity and 72 controls). Blood pressure was measured, and anthropometric parameters were assessed in all included children and adolescents. Fasting lipid profile, fasting glucose, and insulin were measured. DNA extraction and ACE I/D polymorphism genotyping were also performed.ResultsObese children had a higher frequency of DD genotype (30% in obese versus 11.1% in controls, P = .01) and D alleles (61.8% in obese versus 48.6% in controls, P = .01). Obese children with hypertension and prehypertension had higher frequency of DD genotype than II genotype and higher D alleles than I alleles. DD genotype and D allele were independently associated with hypertension (OR: 9.86 and 11.57, respectively, P < .001), while dyslipidemia and insulin resistance were not associated with the ACE I/D gene polymorphism.ConclusionDD genotype and D-allele of the ACE gene polymorphism were associated with obesity and with hypertension and pre-hypertension in Egyptian children.

Effects of angiotensin converting enzyme gene polymorphism on hypertension in Africa: A meta-analysis and systematic review.

BackgroundHypertension is dramatically increasing in Africa with evidence of increased severity and resistance to treatment. Although angiotensin converting enzyme gene polymorphism is associated with higher prevalence of hypertension, the evidence is inconclusive on its influence on the emerging pattern in Africa. This meta-analysis is conducted to pool the available evidence to inform future research and interventions.MethodsArticles published through May 2018 were systematically searched in PubMed, Scopus and EMBASE databases. Studies were assessed for inclusion by two independent researchers. Six models were used to assess the effect of angiotensin converting enzyme deletion-insertion gene polymorphism. Heterogeneity and publication bias were tested and sensitivity analysis was carried out. Odds ratio and 95% confidence intervals were measured for pooled effect. Both random effect and fixed effect models were used, whilst the frequency of DD, II and DI genotypes were computed and compared.ResultPatients with D allele were 1.49 times more likely to develop essential hypertension compared with patients who carry the I allele (OR:1.49; CI:1.07, 2.07). Similarly, patients who had homozygous co-dominance genotype DD (i.e., DD vs II) were at a 2.17 times higher risk of essential hypertension compared to the co-dominant genotype II (OR:2.17, CI:1.79, 3.18), dominant model (I.e., DD+ID vs II) (OR:1.48; CI:1.03, 2.12), and recessive model (OR:1.64; CI:1.03, 2.61). On subgroup analysis, participants from Sub-Saharan Africa were more genetically susceptible to hypertension compared to their North Africa counterparts. There was no publication bias found, but there was high to moderate heterogeneity.ConclusionACE I/D polymorphism is associated with essential hypertension in Africa in the allele contrast model, as well as the dominant, recessive and homozygous codominance model. On subgroup analysis, ACE I/D was associated with essential hypertension in patients from Sub-Saharan Africa but not in North Africa. A future large scale study, which includes different ethnic groups, is recommended.

A deletion mutation within the ATBF1 gene is strongly associated with goat litter size

AT motif-binding factor (ATBF1) is a transcription factor that suppresses carcinogenesis and induces neuronal differentiation, as well as it directly interacts with estrogen receptor (ER) and regulates progesterone receptors signaling. Thus ATBF1 gene will possibly greatly affect reproductive tratis in animals. According to our available findings, two indel (insertion/deletion) variants (12-bp indel; 6-bp indel) within the ATBF1 gene were found in Shaanbei White cashmere goats (SWCG). The objective of this work was to investigate their association with litter size in Shaanbei White Cashmere goat. The association analyses uncovered that ATBF1-12bp indel was strongly related to the first-birth litter size in SWCG population (n = 1195, P = 1.0 × 10−3). Individuals with DD genotype (n = 445) had the best litter size when compared with those of ID genotype (n = 420) and DD genotype (n = 330). Besides, Chi-square tests of different litter size individuals showed that multi-kids individuals had higher “D” allelic frequencies and “DD” genotypic frequencies (p < 0.01). These findings suggested the ATBF1-12bp deletion mutation was significantly associated with reproduction-related trait, suggesting that this deletion could be used as an effective molecular marker for litter size in goat breeding.

ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma.

Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients.Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro.Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; p < 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (p = 0.026).Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.

ACE/ACTN3 GENETIC POLYMORPHISMS AND ATHLETIC PERFORMANCE OF FEMALE SOCCER PLAYERS`

ABSTRACT Objective: Previous studies have shown controversial relationships between ACE and ACTN3 gene polymorphisms and sports performance. Thus, the aim of our study was to assess anaerobic and aerobic performance indicators of young female soccer players with different ACE/ACTN3 gene profiles. Methods: Twenty-seven female soccer players aged 16-18 underwent acceleration, speed, strength, anaerobic power and aerobic endurance tests and had their ACE and ACTN3 polymorphisms determined. Results: Based on genetic analysis, they were divided into the following groups: ACE II (n=2), ACE ID (n=11), ACE DD (n=14), ACTN3 XX (n=5), ACTN3 RR (n=7) and ACTN3 RX (n=15). ACE DD and ACE ID groups differed significantly in terms of results achieved on the 5 m sprint test (1.15±0.05 s vs 1.10±0.05 s, P=0.42). ACTN3 RR and RX achieved better results than the ACTN3 XX group in seven continuous vertical jumps (26.57±1.59 cm vs 25.77±2.51 cm vs 22.86±1.16 cm, respectively; P=0.007 for RR vs XX and P=0.021 for RX vs XX). Conclusion: High prevalence of ACE DD and ACTN3 RX genotypes in our subjects may suggest that faster and more powerful young females tend to perform better in soccer. Nevertheless, the absence of differences in most of the physical test results indicates that different genotypes are compatible with high-level soccer performance, meaning that it is the phenotype-genotype interaction that makes a successful female soccer player. Level of Evidence I, Prognostic studies — Investigating the effect of a patient characteristic on disease outcome.

Genetic Aspects of Preeclampsia: The Role of Polymorphisms in the Genes of the Renin-Angiotensin System.

Preeclampsia (PE) is a severe complication that develops in 10% pregnant women. It is the leading cause of maternal and perinatal morbidity and mortality worldwide. The goal of this study was to reveal the frequency of polymorphisms in the angiotensin-converting enzyme gene (ACE I/D) and type 1 angiotensin II receptor gene (AGTR1 A1166C) in pregnant women with severe early- and late-onset PE. A retrospective case-control study of 55 pregnant women with PE (main group) and 30 patients with uncomplicated pregnancy (control group) was conducted. In the main group, we considered two subgroups - early-onset PE (20 patients) and late-onset PE (36 patients). The I/D polymorphism of the ACE gene is associated with the risk of developing PE. The presence of the D allele increases the risk of severe PE. In case of DD genotype, the probability of early-onset PE is 5 times higher than that of the late-onset PE. The analyzed data confirm the involvement of renin-angiotensin system in the PE development. We conclude that the ACE gene polymorphism is a genetic predictor of the early-onset severe PE. Studying the polymorphic loci of the ACE gene makes it possible to use them for the individualized prognosis of the development and course of PE in patients.

Association of APOBEC3 deletion with cancer risk: A meta-analysis of 26225 cases and 37201 controls.

Previous studies have found inconsistent results regarding gene deletion in APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) and risk of cancer. We conducted a meta-analysis of all eligible case-control studies to find out the associations between APOBEC3 deletion and cancer risk by pooling the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Overall, the findings from 20 studies (13 articles) involving of a total of 26225 cases and 37201 controls revealed that DD genotype was associated significantly with increased cancer risk compared to II genotype (OR=1.25, 95% CI=1.01-1.56, P=0.04). Stratified analysis from 10 studies including 14757 cases and 17930 controls revealed that I/D variant significantly increased the risk of breast cancer in heterozygous codominant (OR=1.15, 95% CI=1.03-1.28, P=0.02, ID vs II), dominant (OR=1.15, 95% CI=1.01-1.31, P=0.03, ID+DD vs II), overdominant (OR=1.11, 95% CI=1.05-1.25, P<0.0001, ID vs DD+II) and allele (OR=1.15, 95% CI=1.13-1.25, P=0.03, D vs I) inheritance models. In conclusion, the data propose that APOBEC3 deletion is significantly associated with increased susceptibility to cancer in overall and breast cancer. Our findings require well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities.