Estimates of the incidence, prevalence, and factors associated with common sexually transmitted infections among Lebanese women.

BACKGROUND: We analyzed the prevalence of active infection with common curable sexually transmitted infections (STIs) including N. gonorrhea, C. trachomatis, T. vaginalis, and T. pallidum, as well as active infection with HPV, herpes simplex virus types I (HSV-1) and II (HSV-2), M. hominis, M. genitalium, C. albicans, and Ureaplasma in 351 Lebanese women. METHODS: A cross-sectional study, involving 351 sexually active women, 40 years or younger, who were recruited from outpatient Obstetrics and Gynecology clinic attendees between September 2016 and November 2017. RESULTS: The prevalence of active infection was low at 0.3% for N. gonorrhea, 0.6% for HSV-2, 2.8% for C. trachomatis, and 2.9% for any curable STIs. Prevalence of active HPV infection was high assessed at 15.7% for high-risk and 12.2% for low-risk genotypes. Furthermore, the prevalence was 2.0% for M. genitalium, 6.8% for ureaplasma, 13.7% for Candida albicans, and 20.5% for M. hominis. No active infections with T. vaginalis, T. pallidum, or HSV-1 were observed. Significant age differences were noted in the prevalence of high-risk and low-risk HPV genotypes, but no such differences were noted in the prevalence of other infections. No appreciable variations were identified in the prevalence of key STIs based on smoking, marital status, or the number of sexual partners. CONCLUSIONS: The study documented active infection with substantial prevalence for multiple STIs among women attending outpatient gynecology and obstetrics clinics in Lebanon. These findings underscore the importance of strengthening STI surveillance, linkage to care, and prevention interventions in reducing STI incidence among women.

Diversity of HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes in Kazakhstani Tatar population and genetic relatedness to other populations.

BACKGROUND: Kazakhstan is a transcontinental former Soviet Union republic whose present-day population comprises more than 100 ethnic groups. Insofar as Human Leukocyte Antigen (HLA) genotyping is useful for anthropological studies, data on the HLA profile of Kazakhstani Tatars are lacking. OBJECTIVE: We extend our earlier findings on the unique HLA profile of distinct Kazakhstani populations by examining HLA class I and class II loci in Kazakhstani (Volga) Tatar minority population and its relatedness to those of bordering and worldwide communities. METHODS: HLA class I and class II genotypes of the Kazakhstan Tatar minority were analyzed by PCR-SSP and were compared to neighboring populations using Neighbor-Joining (NJ) trees and standard genetic distances (SGD) analysis. RESULTS: In total, 132 HLA alleles were identified in a sample of 103 Kazakhstani Tatars, of which HLA-A*02:01 (20.1 %), -B*07:02 (12.1 %), -C*07:02 (12.7 %), -DRB1*07:01 (18.1 %), and -DQB1*02:01 (19.6 %) were the most frequent. The most frequent two-locus haplotypes were B*07:02 âˆ¼ C*07:02 (10.6 %) B*07:02 âˆ¼ DRB1*15:01 (06.1 %), B*07:02 âˆ¼ DQB1*06:02 (07.1 %), and DRB1*15:01 âˆ¼ DQB1*06:02 (11.6 %). CONCLUSIONS: Considering historical data, the close relatedness of Kazakhstani Tatars to European Russians (including Russian Tatars) suggests that Kazakhstani Tatars may be Russian Tatars, who originated from the Volga region, following their massive migrations to central Asia.

Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population-based cohort analysis during 2014-2019 using the national electronic healthcare system.

INTRODUCTION: Spontaneous pregnancy loss (SPL) is a common health problem that affects 1:10 of childbearing women, and is linked with physical and psychological complications. As the number of nationwide studies on the incidence of SPL is few, especially from middle-income countries, in this study we investigated the epidemiology, complications and outcomes of SPL before 22 weeks of gestation by analyzing large-scale healthcare data from the Unified Nationwide Electronic Healthcare System (UNEHS) in Kazakhstan. MATERIAL AND METHODS: A population-based study among women who experienced SPL in any healthcare setting of the Republic of Kazakhstan during the period of 2014-2019. The International Classification of Diseases (ICD) 10th edition and ICD 9th edition's procedural codes were utilized to retrieve data using relevant diagnostic and procedural codes. RESULTS: In total, 207 317 records of women who have experienced an SPL before 22 weeks of gestation were analyzed from all Kazakhstani regions. The estimated prevalence of SPL was 8.7%, with a 20% decline over a 6-year period. The SPL cases ratio comprises on average 6.2 per 1000 reproductive-age women. Incomplete miscarriage (ICD-10 code "O03.4") was the most common type (37.8%), followed by blighted ovum (ICD-10 code "O02.0"; 34.1%) and missed abortion (ICD-10 code "O02.1"; 13.5%). The most common management methods were dilation and curettage of the uterus (ICD-9 code "69.0"; 84.7%) and aspiration curettage of the uterus (ICD-9 code "65.0"; 15%), whereas medical management was rarely performed (2.6%). CONCLUSION: The information available in UNEHS adequately identifies types of miscarriages and treatment methods. Although the prevalence of SPL before 22 weeks of gestation is decreasing, management of miscarriages requires closer attention.

The effects of sildenafil citrate on intrauterine growth restriction: a systematic review and meta-analysis.

BACKGROUND: An increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies. METHODS: Meta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model. RESULTS: Nine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups. CONCLUSION: Sildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission. TRIAL REGISTRATION: The study was registered in PROSPERO on September 18, 2021 (CRD42021271992).

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box.

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study.

BACKGROUND: A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. AIM: To investigate the association of rs34124816 (-537A>C), rs1862513 (-420C>G), rs3219175 (-358G>A), rs3745367 (+299G>A), rs3745369 (+1263G>C), and rs1423096 (+4965C>T) RETN SNPs with PCOS. METHODS: Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real-time PCR. RESULTS: Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor-allele homozygotes and rs1423096 minor-allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor-allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major-allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor-allele-containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six-locus (rs34124816-rs1862513-rs3219175-rs3745367-rs3745369-rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. CONCLUSIONS: This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.

Evaluation of the angiogenic factors sFlt-1, PlGF, and the sFlt-1/PlGF ratio in preeclampsia and associated features.

PROBLEM: Soluble Fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF) were previously reported to play a key role in the pathogenesis of preeclampsia (PE). We tested the link between altered PlGF and sFLT-1 levels, and their ratio (sFlt-1/PlGF) with PE and PE-associated featured in Tunisian PE cases and age- and BMI-matched normotensive women. METHOD OF STUDY: Peripheral blood specimens from 88 women with PE, and 60 control women were tested for PlGF and sFLT by commercially available ELISA. RESULTS: Significant increases in sFlt-1 levels and in the sFlt-1/PlGF ratio, more than changes in PlGF levels were noted in PE subjects when compared to control women. Elevation in sFlt-1 and sFlt-1/PlGF ratio was observed at different percentile values in PE cases. The receiver operating characteristic (ROC) area under the curve (AUC) for sFlt-1, PlGF, and sFlt-1/PlGF ratio were 0.869 ± 0.031, 0.463 ± 0.048, and 0.759 ± 0.039, respectively. A systematic shift in sFlt-1, but not in PlGF, distributions for higher values occurred in PE subjects. A progressive increase in the adjusted OR paralleled increased sFlt-1 and the sFlt-1/PlGF ratio percentile values; no similar trend was noted for the PlGF percentiles. Increased sFlt-1 levels and sFlt-1/PlGF ratio were significantly correlated with dysmenorrhea, hypertension, baby weight, and C-section. In contrast, no correlation was found between PlGF and the PE-associated features tested. CONCLUSIONS: Increased sFlt-1 levels and corresponding sFlt-1/PlGF ratio, but not circulating PlGF levels, constitute an independent risk factor for PE.

Analysis of the Origin of Emiratis as Inferred from a Family Study Based on HLA-A, -C, -B, -DRB1, and -DQB1 Genes.

In this study, we investigated HLA class I and class II allele and haplotype frequencies in Emiratis and compared them to those of Asian, Mediterranean, and Sub-Saharan African populations. METHODS: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis. RESULTS: The studied HLA loci were in Hardy-Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations. CONCLUSIONS: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis' gene pool appears to be minor.

Knowledge and attitudes of mothers toward HPV vaccination: A cross-sectional study in Kazakhstan.

BACKGROUND: Although recommended for all member states of World Health Organization, there is no national human papillomavirus vaccination program in Kazakhstan. Furthermore, there are no studies in Kazakhstan that evaluate the mothers' perception of human papillomavirus vaccines. OBJECTIVES: This study aims to assess the knowledge and attitudes toward human papillomavirus vaccination among mothers in Kazakhstan and the factors associated with their attitudes. DESIGN: A cross-sectional study was performed during the period of December 2021-February 2022. The STROBE guideline for cross-sectional studies was applied. METHODS: Paper-based structured questionnaires were filled out by 191 mothers, 141 of whom had daughters. The attitude score was assessed as per the Likert-type scale. The Chi-square and Fisher's exact tests, with a significance value of < 0.05 were used to analyze the relationships between the characteristics of mothers and their attitude scores. RESULTS: The following factors were significantly associated with mothers' attitudes toward human papillomavirus vaccination: a place of residence, family income, number of children, and refusal of vaccination for themselves (p < 0.005). Of all participants, only 45% of all mothers, 41% of mothers with a female, and 46% of mothers with male children had positive attitudes toward human papillomavirus vaccination. The child's gender was not a significant determinant. Overall, the level of knowledge about human papillomavirus vaccination was found to be low. The median total score is 0 out of 12 for women who have negative and neutral attitudes toward human papillomavirus vaccines. Among women who have positive attitudes toward HPV vaccines, the median score is around 3 points. CONCLUSION: Before the implementation of the human papillomavirus vaccination program into the Kazakhstani national vaccination calendar, comprehensive and adequate information and education campaigns are required on the national level for parents and the population in general.

Preeclampsia is associated with reduced renin, aldosterone, and PlGF levels, and increased sFlt-1/PlGF ratio, and specific angiotensin-converting enzyme Ins-Del gene variants.

We investigated the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with preeclampsia (PE) in Tunisian women. ACE I/D genotyping was done by PCR in 342 pregnant women with PE and 289 healthy pregnant women. The association between ACE I/D and PE and associated features were also evaluated. Decreased active renin concentration, plasma aldosterone concentration, and placental growth factor (PlGF) were observed in PE cases, while soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio was significantly higher in the PE group. Distribution of ACE I/D alleles and genotypes were comparable between women with PE and control women. A significant difference in the frequency of the I/I genotype was seen between PE cases and control women according to the recessive model, with a trend towards association in the codominant model. Carriers of the I/I genotype had significantly higher infant birth weights compared to the I/D and the D/D genotype carriers. A dose-dependent relationship was also seen in VEGF and PlGF plasma levels and specific ACE I/D genotypes, with the lowest VEGF levels seen in the I/I genotype carriers compared to the D/D genotype carriers. Similarly, the I/I genotype carriers had the lowest PlGF levels compared to I/D and D/D genotype carriers. Furthermore, when studying the linkage between PE features, we found a positive correlation between PAC and PIGF. Our study suggests a role for ACE I/D polymorphism in the pathogenesis of PE, possibly through modulating VEGF and PlGF levels and infant birth weight, and highlights the relationship between PAC and PlGF.

Differential Association of FTO Gene variants and Haplotypes with the Susceptibility to Polycystic Ovary Syndrome According To Obesity in Women with PCOS.

We explored the relation between FTO single gene variants (rs1861868, rs9939973, rs1421085, rs1121980, rs17817449, rs8050136, rs9939609, rs9930506, and rs8044769) and polycystic ovary syndrome (PCOS), in particular, according to the obesity status. This retrospective population-based case-control study involved women with PCOS (583) and 713 eumenorrheic control women; genotyping was done by real-time PCR. Significantly higher minor allele frequency (MAF) of rs9939973, rs17817449, rs9939609, and rs9930506 and lower MAF of rs1121980 were seen in PCOS cases. Lower risk of PCOS was associated with rs1121980 and rs8050136 heterozygous and minor allele-homozygous genotypes, while an elevated risk of PCOS was seen with minor allele-homozygous rs9939973, rs17817449, and r9939609 heterozygous and genotypes and minor allele-homozygous rs9930506 and rs8044769 genotype. While none of the tested FTO SNPs variants was associated with PCOS in normal body weight/lean subjects, rs9939973, rs9939609, and rs9930506 were negatively associated with PCOS in overweight subjects. In comparison, rs1861868 was negatively, while rs8044769 was positively associated with PCOS in obese subjects. Haplotype analysis identified haplotypes GACCTCTAT, AACCTCTAT, AACCTATAT and AGTTGCAGC, and GACCTCTAC to be positively associated with PCOS, while haplotypes GGTTGAAGC, GACCTATAT, GGTTGCAGC, and GATCTATAT were negatively associated with PCOS. Apart from GGTTGAAGC, these haplotypes remained associated with altered risk of PCOS after adjusting for covariates. In addition to rs17817449, rs9939609, rs9930506, and rs1121980, this study is the first to demonstrate association of rs9939973 and rs8044769 with altered risk of PCOS and the first to confirm the BMI dependency on the association of FTO variants with PCOS. This underscores the role of FTO gene variants as predisposing factors of PCOS.

Novel Association of IGF2BP2 Gene Variants With Altered Risk of Breast Cancer and as Potential Molecular Biomarker of Triple Negative Breast Cancer.

BACKGROUND: Several studies documented that insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) contributes to carcinogenesis, and 1 report documented the association of IGF2BP2 rs4402960 with increased risk of breast cancer (BC). This study investigated the association of rs4402960 and rs1470579 IGF2BP2 variants with BC and triple negative BC (TNBC). MATERIALS AND METHODS: This case-control study included 488 BC patients comprising 130 TNBC and 358 non-TNBC patients, and 476 cancer-free controls. Genomic DNA was obtained from peripheral venous blood, and genotyping was done by allelic exclusion method on real-time PCR. RESULTS: The rs440960, but not rs1470579, minor allele was significantly associated with BC, and significantly higher rs4402960 T/T genotype frequency was noted in BC patients than controls; the distribution of rs1470579 genotypes were comparable between BC patients and controls. In contrast, significantly lower rs1470579 minor allele frequency, and reduced rs1470579 A/C and C/C, and rs4402960 T/T genotype frequencies were seen in TNBC cases. Among TNBC cases, rs4402960 and rs1470579 correlated with menses pattern, histological type, breastfeeding, oral contraceptive use and hormonotherapy. Among non-TNBC patients, and rs1470579 correlated significantly with breast feeding, oral contraceptive use, hormonotherapy, and nodal status; rs4402960 also correlated with menses pattern. Two-locus (rs440960-rs1470579) haplotype analysis confirmed the positive association of TC, and negative association of GC and TA haplotypes with BC, while TC and GC haplotypes were negatively associated with TNBC. CONCLUSION: Whereas rs440960 was positively associated with BC, both rs4402960 and rs1470579 were negatively associated with TNBC, suggesting potential diagnostic/prognostic role in BC and its complications.

Depression, Anxiety, and Stress in Kazakhstani Women with Recurrent Pregnancy Loss: A Case-Control Study.

Background: Recurrent pregnancy loss (RPL) is associated with increased incidence and severity of depression, anxiety, and stress, and screening for these comorbidities following miscarriages is beneficial for women with RPL who are planning future pregnancies. This study aims to investigate depression, anxiety, and stress among Kazakhstani women with RPL. Methods: This was a case−control study involving 70 women with confirmed RPL and 78 ethnically matched control women. Depression, anxiety, and stress were evaluated using the Depression Anxiety Stress Scales (DASS)-21 instrument. Linear regression and correlation analysis were used in assessing the association of RPL with symptoms of depression, and/or anxiety, and/or stress, after adjusting for key covariates. Results: Women with RPL were found to have significantly higher mean scores for depression (p < 0.001), anxiety (p < 0.001), and stress (p < 0.001) symptoms. Mild−moderate stress and mild−moderate and severe−extreme depression and anxiety symptoms were more frequent in the RPL group than in the control group. Regression analysis demonstrated that RPL was the only significant variable associated with anxiety, depression, and stress symptoms. Conclusion: The results of this study suggest that women with RPL are more likely to experience heightened symptoms of depression, anxiety, and stress. Proper psychological counseling is recommended for women with RPL, as well as their spouses.

Genetic diversity of human papillomavirus (HPV) as specified by the detection method, gender, and year of sampling: a retrospective cross-sectional study.

PURPOSE: This study assesses HPV prevalence and genotype distribution in Lebanon, and identifies differentials in HPV infection, infection with multiple genotypes, and with high-risk genotypes, by sex, age, and year of data collection. METHODS: Study participants comprised 1042 female and 160 male participants between 2006 and 2018. HPV genotyping was done by PCR and hybridization (2006-2013) or real-time PCR (2013 onwards). Diversity of HPV genotypes across gender, age groups, and years of data collection was tested by applying Shannon Diversity Index. RESULTS: The overall HPV prevalence was 44.8% among study participants, and threefold higher in women than men. Single HPV infection was seen in two-third of HPV-positive participants. Women were less likely to be infected with multiple HPV strains, but more likely to be infected with high-risk or mixed-risk HPV genotypes. HPV-16 (11.0%, 9.8%) and HPV-53 (8.5%, 4.9%) were the most prevalent high-risk HPV genotypes in women and men, respectively, while HPV-18 prevalence was 4.9% in men and 3.1% in women, while HPV-59 prevalence was 6.6% in men and 2.1% in women. Samples collected post-2011 from women showed twice higher odds of HPV infection than those collected earlier and were threefold more likely to be infected with multiple HPV strains, and twice more likely to be infected with high-risk genotypes compared to those tested earlier. Women scored higher on Shannon index indicating high diversity in HPV types and frequency, with trend of increased diversity over time. While the odds of HPV infection remained associated with sex and temporal trend in multivariable analysis, odds of having high-risk genotypes was mainly associated with infection with multiple HPV strains. CONCLUSION: Our study showed high diversity in HPV genotypes and an increasing trend of infection with multiple and high-risk genotypes in recent years. Findings underscore the need for effective screening/surveillance and HPV vaccination programs.

Unique ESR1 and ESR2 estrogen receptor gene variants associated with altered risk of triple-negative breast cancer: A case-control study.

BACKGROUND: We previously reported on the association between ESR1 and ESR2 gene variants and heightened risk of breast cancer (BC). Here we investigated the association of common ESR1 and ESR2 gene variants with triple negative BC (TNBC). METHODS: This retrospective case-control study involved 488 BC patients (130 TNBC, 358 non-TNBC patients). ESR1 (rs2234693, rs9340799, rs3020314, rs3798577) and ESR2 (rs928554, rs944459, rs4986938, rs1256049, rs1256030, rs1271572) genotyping was done by real-time PCR. RESULTS: While minor allele frequencies (MAF) of ESR1 variants were comparable between TNBC and non-TNBC subjects, significantly higher ESR2 rs1256049 MAF was seen in TNBC patients. Significantly higher frequency of ESR1 rs3798577 T/C and C/C genotypes were noted in TNBC cases, and significant differences were seen in ESR2 rs928554, rs1256049, and rs1271572 genotype distribution. Increased TNBC risk was associated with ESR1 rs3798577 T/C and C/C genotypes according to codominant and dominant models, while positive association of ESR2 rs928554 with TNBC was seen according to codominant and recessive models, and positive association of ESR2 rs1256049 with TNBC was seen according to codominant and dominant models. Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC. CONCLUSION: Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.

HLA allele and haplotype frequencies in Kazakhstani Russians and their relationship with other populations.

HLA class I and class II genotypes from 947 Kazakhstani individuals of Russian origin were analyzed for investigating their most likely origin. The results were compared with similar data from other Russians (East and West), and also Worldwide populations, using standard genetic distances, neighbor-joining dendrograms, correspondence and haplotype analysis. Of the five HLA loci analyzed (HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1) genotyped, 216 HLA alleles were identified. The most frequent alleles were A*02:01 (26.5%), B*07:02 (11.1%), C*04:01 (13.5%) and C*06:02 (12.1%), DRB1*07:01 (13.8%) and DRB1*15:01 (12.2%), and DQB1*03:01 (19.7%). Significant linkage disequilibrium was noted between all HLA pairs. DRB1*15:01 ~ DQB1*06:02 (10.5%), B*07:02 ~ C*07:02 (10.0%), B*07:02 ~ DRB1*15:01 (6.3%), and A*01:01 ~ B*08:01 (4.5%) were the most frequent two-locus haplotypes identified. Subsequent analyses showed that Kazakhstani Russians were closely related to West Russia-residing populations (Northwest Slavic, Vologda, Chelyabinsk, Moscow), East Europeans (Belarus Brest, Ukraine, Poland) and Scandinavians (Swedish, Finns), but distinct from East Russia-residing populations (Tuvians, Siberians from Chukotka, Kamchatka, and Ulchi) and East Mediterraneans (Levantines, Turks, North Macedonians, Albanians), and East Asians (Koreans, Japanese, Taiwanese, Mongolians). These results are in accordance with historical data indicating that the Russians of central Asia originate mainly from European Russia during the migratory flow of 18th and 19th centuries.

Relation of CRP gene variants to altered risk of Helicobacter pylori - associated chronic gastritis: A case-control study in Tunisia.

BACKGROUND: We investigated the association between CRP variants and chronic gastritis in H. pylori-infected patients at the allele, genotype, and haplotype levels. This was also assessed according to serum hs-CRP levels. METHODS: Study subjects consisted of 77 H. pylori-infected patients and 96 H. pylori-negative controls. Genotyping of the CRP rs1572970, rs876537, rs2794520, rs2808630, rs1130864, rs1417938, rs7553007, and rs4285692 variants were analyzed by real-time PCR. RESULTS: Significantly higher MAF and increased risk of chronic gastritis were associated with rs1130864, rs1417938, and rs7553007, which persisted after controlling for key covariates. Significant differences in the genotype distribution of rs1130864, rs1417938, and rs7553007 were also seen between H. pylori-infected patients and healthy controls. Increased risk of H. pylori-associated chronic gastritis was associated with carriage of rs1130864 C/T, and more with T/T genotype carriers, as well as with rs1417938 T/A and A/A genotype carriers. Functionally, the distribution of rs1130864 and rs1417938 genotypes were significantly different between H. pylori-infected patients and controls in the low hs-CRP (<6 mg/L) group. CRP haplotype analysis identified Block 1 (rs1572970, rs876537, rs2794520), and Block 2 (rs2808630, rs1130864, rs1417938) associated with H. pylori infection. Haplotypes ACC (Block 1) and TTA and TTT (Block 2) were positively associated with H. pylori-associated chronic gastritis with low hs-CRP levels. CONCLUSION: Altered serum levels of hs-CRP, stemming in part from the presence of specific genetic variants in CRP gene, modulate the risk of H. pylori infection.

ADIPOQ gene polymorphisms and haplotypes linked to altered susceptibility to PCOS: a case-control study.

RESEARCH QUESTION: What role do ADIPOQ variants play in controlling adiponectin concentrations and altered risk of polycystic ovary syndrome (PCOS)? DESIGN: Study subjects comprised 583 women with PCOS and 713 age-matched controls. Genotyping of rs182052, rs822393, rs822396, rs7649121, rs3774271, rs266729, rs3774261 and rs6773957 ADIPOQ polymorphisms was done by real-time polymerase chain reaction (PCR). RESULTS: Of the 16 ADIPOQ variants, the minor allele frequencies of rs182052, rs822393, rs822396, rs7649121, rs3774261 and rs6773957 were significantly different between PCOS cases and controls. Significant differences in rs266729 (P = 0.02), rs822396 (P = 0.02), rs3774261 (P < 0.001) and rs6773957 (P < 0.001) genotypes were also noted between PCOS cases and controls. Reduced PCOS risk was found with heterozygous rs266729, while increased risk was linked to heterozygous rs822396 and homozygous minor allele rs3774361, and in heterozygous and homozygous minor allele rs6773957 genotype carriers. Haplotype analysis identified two blocks based on linkage disequilibrium pattern; alleles coded as '1' (major) and '2' (minor). Within Block 1 (rs4632532, rs16861194, rs266729, rs182052, rs16861209, rs822393, rs822395, rs822396, rs7649121), haplotypes 111111111 and 212211221 were positively, while haplotypes 212212112 and 212211211 were negatively associated with PCOS. Within Block 2 (rs2241766, rs1501299, rs2241767, rs3774261, rs6773957, rs1063539) haplotypes 111221 and 112221 were positively, while haplotype 111111 was negatively associated with PCOS. CONCLUSIONS: This is the first study to confirm the association of rs182052, rs822393, rs7649121 and rs6773957 ADIPOQ variants with altered risk of PCOS. The varied association of ADIPOQ variants with PCOS in relation to earlier reports indicate there is an ethnic contribution to ADIPOQ association with PCOS.

miR-146a, miR-196a2, miR-499, and miR-149 linked with susceptibility to acute lymphoblastic leukemia: A case-control study in Tunisia.

BACKGROUND: MicroRNAs (miRNAs) are promising biomarkers of hematological malignancies, including acute lymphoblastic leukaemia (ALL). Recent studies revealed that miRNA single nucleotide polymorphisms (miR-SNP) modulate cancer risk by regulating various signaling pathways. However, their association with altered risk of ALL yielded inconsistent results. OBJECTIVE: This study aims to investigate the association of four miR-SNPs with altered risk of ALL risk in Tunisian, the first on North African population. METHODS: A retrospective case-control study exploring the association of miR-146a, miR-196a2, miR-499, and miR-149 SNPs in 126 ALL patients and 126 healthy controls. RESULTS: Of the tested variants, significantly lower minor allele frequencies (MAF) of miR-146a C-allele and higher MAF frequency of miR-149 T-allele (P = 0.006) were seen in ALL cases. The association of miR-149 rs2292832 (Pc = 0.02), but not miR-146a rs2910164 (Pc = 0.11) persisted after correcting for multiple comparisons. Significantly reduced prevalence of miR-146a G/C genotype and higher frequency of miR-149 C/T genotype were seen in ALL cases vs. control subjects, which translated into negative association of miR-146a (rs2910164) with ALL according to the codominant and dominant models. Similarly, miR-149 (rs2292832) was positively associated with ALL according to the codominant and dominant genetic models. Three combinations comprising miR-146a/miR-196a2 GG vs CT + TT genotype combination, miR-146a/miR-499 GG vs TC + CC genotype combination, and miR-146a/miR-149 GG vs CT + TT genotype combination, were less frequent in ALL patients than in controls, and were negatively associated with the presence of ALL. CONCLUSION: Our study suggests that miR-146a and miR-149 polymorphisms constitute biomarkers for personalized diagnosis of ALL.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in Lebanese and their relatedness to neighboring and distant populations.

BACKGROUND: This study examined the origin of present-day Lebanese using high-resolution HLA class I and class II allele and haplotype distributions. The study subjects comprised 152 unrelated individuals, and their HLA class I and class II alleles and two-locus and five-locus haplotypes were compared with those of neighboring and distant communities using genetic distances, neighbor-joining dendrograms, correspondence, and haplotype analyses. HLA class I (A, B, C) and class II (DRB1, DQB1) were genotyped at a high-resolution level by PCR-SSP. RESULTS: In total, 76 alleles across the five HLA loci were detected: A*03:01 (17.1%), A*24:02 (16.5%), B*35:01 (25.7%), C*04:01 (25.3%), and C*07:01 (20.7%) were the most frequent class I alleles, while DRB1*11:01 (34.2%) and DQB1*03:01 (43.8%) were the most frequent class II alleles. All pairs of HLA loci were in significant linkage disequilibrium. The most frequent two-locus haplotypes recorded were DRB1*11:01 ~ DQB1*03:01 (30.9%), B*35:01-C*04:01 (20.7%), B*35:01 ~ DRB1*11:01 (13.8%), and A*24:02 ~ B*35:01 (10.3%). Lebanese appear to be closely related to East Mediterranean communities such as Levantines (Palestinians, Syrians, and Jordanians), Turks, Macedonians, and Albanians. However, Lebanese appear to be distinct from North African, Iberian, and Sub-Saharan communities. CONCLUSIONS: Collectively, this indicates a limited genetic contribution of Arabic-speaking populations (from North Africa or the Arabian Peninsula) and Sub-Saharan communities to the present-day Lebanese gene pool. This confirms the notion that Lebanese population are of mixed East Mediterranean and Asian origin, with a marked European component.