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This article examines the daily routine in crisis accommodation for young women in Poland, investigating the hidden curriculum that includes highly gendered norms and expectations regarding residents. The article considers local crisis centres and state-funded Specialist Centres for Victims of Domestic Violence as well as Single Mothers' Homes, which provide long-term accommodation for mothers with dependent children. The analysed material has been gathered during fieldwork in Warsaw and the Podkarpackie province in the Years 2017–2018 and comprises diverse data types: interviews with managers and staff at crisis centres and Single Mothers' Homes; legal acts that regulate referrals as well as house rules adopted in these facilities. The residents were interviewed about their experiences of, and views on their daily routines, tasks and relationships within shelters. In crisis centres, expectations are focussed on self-sufficiency, while in Catholic Single Mothers' Homes, control is exercised through religion by defining what is proper behaviour and how a mother should behave. The article concludes by investigating these practices with regard to their effectiveness in supporting women's housing needs and examining how they relate to a broader definition of social work. [ABSTRACT FROM AUTHOR]

It has been a couple of decades since attempts have been made to measure the extent of homelessness at national levels in Europe. While these counts are essential for public policymaking, producing such statistics also (re)produces power-knowledge. The definitions and categories used in homelessness surveys indicate how it is understood as a social problem. In Europe, the Nordic countries have some of the most reliable and current figures on homelessness. On the other hand, the Polish national homelessness count is highly criticized. This study compared the definitions, methodologies, and formats used in homelessness surveys from Denmark, Norway, Sweden, and Poland. This investigation involved analyses of the way counts were organized, the categories used, and the creation of reports based on homelessness data. This enabled a deconstruction of how welfare states have used these numbers as metaphors and evidence to frame homelessness as a manageable phenomenon. [ABSTRACT FROM AUTHOR]

Objective: The etiology of non‐syndromic cleft lip with or without cleft palate (nsCL/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare PAX7 nucleotide variants and the risk of this common congenital anomaly in a Polish population. Subjects and methods: Eight top nsCL/P‐associated PAX7 variants identified in our cleft genome‐wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (n = 247 and n = 445, respectively). In addition, mutation screening of the PAX7 protein‐coding region was conducted. Results: Analysis of the pooled data from the GWAS and replication study confirmed that common PAX7 nucleotide variants are significantly associated with the increased risk of nsCL/P. The strongest individual variant was rs1339062 (c.586 + 15617T > C) with a p‐value = 2.47E−05 (OR = 1.4, 95%CI: 1.20–1.64). Sequencing analysis identified a novel synonymous PAX7 substitution (c.87G > A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements. Conclusion: Our study confirmed that PAX7 is a strong candidate gene for nsCL/P. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population. [ABSTRACT FROM AUTHOR]

Objective: The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. Subjects and Methods: Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). Results: The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.‐1‐21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76–1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. Conclusion: Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly. [ABSTRACT FROM AUTHOR]

The article focuses on the requirements reflected in legal acts as well as on the organisational conditions connected with the conduct of film education in both schools and cultural institutions in Poland. The above issues allowed the author to draw attention to the possibilities, but also limitations and therefore real problems, connected with the practice of carrying out film education of children and young people in Poland. The final part of the text provides a brief insight into the possible place of film education in the country's school system, which is currently being reformed. [ABSTRACT FROM AUTHOR]

Purpose: Endometriosis is considered to be an estrogen-related chronic inflammatory disease. The 17β-hydroxysteroid dehydrogenase 1 (HSD17B1) converts estrone to 17β estradiol. The role of HSD17B1 937 A>G (rs605059) single nucleotide polymorphism (SNP) in development of endometriosis is still disputable. This study evaluated the association of the HSD17B1 937 A>G (rs605059) SNP with infertile women affected by endometriosis from Polish Caucasian population. Methods: The genotyping of cases ( n = 290) and fertile women ( n = 410) was conducted by high-resolution melting curve analysis. Results: Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with endometriosis in stages I and II. The p and p values calculated for the HSD17B1 937 A>G polymorphism were statistically significant and were equal to 0.001 and 0.0009, respectively. There was a significant association for the dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178-3.304), p = 0.009, and for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178-2.770), p = 0.006 . However, we did not find statistical association of HSD17B1 937 A>G polymorphism with all infertile women with endometriosis or infertile women with endometriosis in stages III and IV. Conclusion: Our genetic study demonstrated HSD17B1 937 G variant as a risk factor for infertility in women with stage I and II endometriosis in Polish Caucasian patients. [ABSTRACT FROM AUTHOR]

Background: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients.Methods: The study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR-RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model.Results: In univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0-7.0 years vs 4.7, 0.1-7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11-3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02-1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival.Conclusions: Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors. [ABSTRACT FROM AUTHOR]

The project "Searching for new genes and loci involved in cleft lip and palate in the Polish population - genome-wide association study" is a case-control study in a group of unrelated subjects with non-syndromic cleft lip with or without cleft palate (NSCL/P) and healthy individuals with no family history of clefting or other congenital disorders. The overall goal of this grant proposal is to identify novel genetic factors, which can play a significant role in the pathogenesis of orofacial clefts in the Polish population. To accomplish the proposed aim, a two stage genome-wide association study will be performed. In the first stage, Illumina's HumanOmni Express BeadChips arrays will be used to genotype over 700,000 polymorphisms in NSCL/P patients and controls. In the second stage, SNPs showing the most compelling association with the risk of orofacial clefts will be tested in an independent sample set using standard genotyping methods. This research project is expected to be completed in July 2015. [ABSTRACT FROM AUTHOR]

Background and Objective: The Wnt/β-catenin signaling pathway has been considered to be a factor in the development and progression of ovarian cancer. Methods: All patients with ovarian cancer and controls were tested for BRCA1 mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers were excluded from the association analysis. We studied nine single nucleotide polymorphisms (SNPs) located in CTNNB1 (β-catenin) [rs4533622, rs2953], APC (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087, rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations ( n = 228) and controls ( n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771, AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the appropriate restriction enzyme digestion [PCR-restriction fragment length polymorphism (PCR-RFLP)]. Results: The most common BRCA1/ BRCA2 mutations were identified in 30 patients with ovarian cancer. These mutations were not found in controls. The lowest p values of the trend test ( p) were observed for the APC rs351771 and rs11954856 SNPs in patients with ovarian cancer ( p = 0.006 and p = 0.007, respectively). Using a dominant inheritance model, we found that the APC rs11954856 SNP is associated with an increased risk of ovarian cancer development [odds ratio = 2.034 (95 % CI 1.302-3.178); p = 0.002]. We also observed significant allelic differences for the APC rs351771 SNP between patients and controls ( p = 0.006). Conclusion: Our study demonstrated significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish women with ovarian cancer. [ABSTRACT FROM AUTHOR]

This article discusses the results of fieldwork conducted among physically homeless Polish migrants in Oslo, Norway. I focus on the social networks that are a part of the migrants' social capital, and which should ideally prevent them from a state of ‘rooflessness’. I present the narratives of these Polish rough-sleepers in Oslo and analyse their links with the home country and their bonds with the Polish community in Norway and with the wider Norwegian society. I focus on the migrants' daily survival strategies, ways of obtaining information about work and accommodation and economical exchanges as indicators of their network links. I distinguish the limitations of migrants' social networks in extricating them from a situation of homelessness. Based on this analysis, a simple typology of the Polish homeless in Oslo is presented—largely comparable with other homeless groups described elsewhere. [ABSTRACT FROM PUBLISHER]

The contribution of the p53 Arg72Pro polymorphism in the development of systemic lupus erythematosus (SLE) remains controversial. We investigated the frequency of the p53 Arg72Pro genotype in patients with SLE (n = 155) and in controls (n = 150) in Poland. We found a weak contribution of the Arg/Arg genotype to the morbidity of SLE. Odds ratio (OR) for patients with SLE and p53 Arg/Arg genotype was 1.875 [95% CI = 1.180-2.979], P = 0.0075 and OR of the Arg/Arg and Arg/Pro genotypes was 1.549 [95% CI = 0.752-3.195], P = 0.2328. Since the p53Arg variant supports apoptosis better than the p53Pro variant, our findings can be linked to an increase in the number of apoptotic leucocytes in SLE patients. The distinction between various populations may be because of differences in racial composition and/or exposure to distinct environmental factors that have a different impact on SLE incidence along with the changed Argp53Pro genotype. [ABSTRACT FROM AUTHOR]

Determining the correct height of mountain peaks is vital for tourism, but it is also important as a reference point for devices equipped with GPS (Global Positioning System), e.g., watches or car navigation systems. The peak altitude data are part of geographic and geodetic information. As more modern technologies and equipment become available, their precisions should increase. However, verification of peak heights is usually only conducted for the highest, well-known mountains—lower peaks or mountain passes are rarely verified. Therefore, this study focuses on an investigation of 12 altitude points on a section of the longest and most famous touristic trail in Poland (the Main Beskid Trail), located in the Orava–Żywiec Beskids Mts (Mountains). The aim of this research is to measure and verify the heights of the 12 selected mountain peaks, in addition to evaluating the chosen methods based on the quality of the obtained data and determining their suitability and opportunities for use in further research. Measurements were obtained at the most specific height points—on the 12 highest points of the summits. This study compares two modern measurement techniques: the global navigation satellite system (GNSS) and light detection and ranging (LiDAR). The obtained results were later compared with those widely used on the internet and in printed materials (period covered: 1884–2015). This analysis demonstrates that lesser-known objects are rarely the subject of remeasurement and significant altitude errors may occur, primarily because the heights originated from a source in the past when modern methods were not available. Our findings indicate that the heights of the peaks presented in cartographic materials are inaccurate. The assumed heights should be corrected by direct measurements using modern techniques. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated an association of the NC_000012.12:g.53962605A > G, (rs2366152) single-nucleotide variant (SNV) situated in the long noncoding homeobox transcript antisense intergenic RNA (HOTAIR) gene with HPV16-related cervical cancer pathogenesis. However, little is known about the role of rs2366152 in cervical cancer progression and how oral birth control pills use, parity, menopausal status, and cigarette smoking influence the role of rs2366152 in cervical carcinogenesis. HRM analysis was used to determine the rs2366152 SNV prevalence in patients with cervical squamous cell carcinoma (SCC) (n = 470) and control group (n = 499) in a Polish Caucasian population. Logistic regression analyses were adjusted for age, using birth control pills, parity, menopausal status, and cigarette smoking. Our genetic studies revealed that the G/A vs. A/A (p = 0.031, p = 0.002) and G/A + G/G vs. A/A (p = 0.035, p = 0.003) genotypes of rs2366152 SNV were significantly related to the grade of differentiation G3 and tumor stage III, respectively. Moreover, cervical cancer risk increased among patients with rs2366152 SNV who smoked cigarettes and used birth control pills. We conclude that rs2366152 may promote the invasion and rapid growth of cervical SCC. Moreover, rs2366152 with cigarette smoking and using birth control pills can also be a risk factor for cervical cancerogenesis., (© 2023. The Author(s).)

Introduction: Hypercholesterolemia is a chronic noncommunicable disease predisposing to cardiovascular diseases. Genome‑wide association studies have shown that more than 500 common nucleotide variants are associated with dyslipidemia., Objectives: We evaluated associations between selected nucleotide variants in ANGPTL6, DOCK6, FABP1, and PCSK9 genes and hypercholesterolemia in the Polish adult population sample., Patients and Methods: The study included 109 patients with hypercholesterolemia and 251 individuals with no diagnosed lipid disorder. Genotyping of ANGPTL6 rs8112063, DOCK6 rs737337 and rs17699089, FABP1 rs2241883 and rs2919872, and PCSK9 rs562556 and rs11206510 was carried out using highresolution melting curve analysis. Serum concentrations of FABP1, PCSK9, ANGPTL6, and ANGPTL8 were determined in 51 individuals by enzyme‑linked immunosorbent assay., Results: Carriers of the FABP1 rs2919872 CC genotype were over 2.5‑fold less likely to be diagnosed with hypercholesterolemia than carriers of the T allele (odds ratio [OR], 0.386; 95% CI, 0.203-0.735; P = 0.003; Pcorr = 0.006). There were no associations between rs2919872 and serum lipid concentrations. Carriers of the ANGPTL6 rs8112063 C allele had an almost 2‑fold higher risk of developing hypercholesterolemia than carriers of the T allele (OR, 1.820; 95% CI, 1.053-3.144; P = 0.03; Pcorr = 0.046). Moreover, the carriers of the ANGPTL6 rs8112063 C allele had higher serum concentrations of high-density lipoprotein cholesterol than those with TT genotype (P = 0.009). There were no significant associations between the other tested variants and hypercholesterolemia., Conclusions: FABP1 rs2919872 and ANGPTL6 rs8112063 are associated with a risk of hypercholesterolemia in the Polish population.

Introduction: Obesity is a complex disease associated with excessive fat accumulation and numerous metabolic complications. So far, many factors leading to the development of this disorder have been identified, including genetic susceptibility. Various studies linked GLP1R variants with anthropometric and metabolic parameters, suggesting the role of the variation in this gene in metabolic health., Objective: The aim of this study is to investigate the association of two single nucleotide variants of GLP1R gene, rs2268641 and rs6923761, with excessive weight, metabolic syndrome, anthropometric measurements and selected metabolic parameters., Methods: Normal-weight subjects (n= 340, control group) and subjects with excessive body mass (n = 600, study group) participated in this study. For all participants, anthropometric measurements and metabolic parameters were collected, and genotyping of the two single nucleotide variants of GLP1R gene, rs2268641 and rs6923761, was performed using the high-resolution melting curve analysis., Results: Significant differences in the genotype distribution of rs2268641 were found, where homozygous TT genotype was significantly less frequent in the study group with excessive body mass (OR=0.66; p=0.0298). For rs6923761, A allele and homozygous AA genotype were significantly more frequent in the study group with excessive weight than in the control group (OR=1.27; p=0.0239 and OR=1.69; p=0.0205, respectively). The association of studied variants with metabolic parameters was found for rs6923761. For this variant, AA carriers had higher body mass in comparison to GG carriers (p=0.0246), and AA carriers had higher glucose concentration in comparison to AG carriers (p=0.0498). We did not find an association of rs2268641 and rs6923761 with metabolic syndrome., Conclusion: In our study, AA carriers of rs6923761 had higher risk of excessive body mass, whereas TT carriers of rs2268641 had lower risk of being overweight. Moreover, homozygous carriers of the minor allele of rs6923761 had higher glucose concentration in comparison to heterozygous subjects. None of the studied variants were associated with metabolic syndrome in the studied population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Michałowska, Miller-Kasprzak, Seraszek-Jaros, Mostowska and Bogdański.)

Background: There is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-associated gene (ENHO), retinoid X receptor α gene (RXRA), and liver X receptor α gene (LXRA)., Methods: The study included 1208 HD subjects. For diagnosis of dyslipidemia, both K/DOQI criteria and atherogenic index ≥3.8 were used. CASR rs1801725 was genotyped by TaqMan SNP Genotyping Assay, other SNPs - by high-resolution melting curve analysis or polymerase chain reaction-restriction fragment length polymorphism, as appropriate. Relative transcript levels of CASR, ENHO, RXRA, and LXRA were measured in peripheral blood mononuclear cells. The occurrence of dyslipidemic phenotypes concerning tested polymorphisms was compared using models of inheritance. Haplotypes were estimated using the Haploview 4.2 software. Epistatic interactions between tested SNPs were analyzed using the logistic regression and epistasis option in the PLINK software., Results: Rs7652589 indicated a greater probability of atherogenic dyslipidemia in the dominant inheritance model (OR 1.4, 95%CI 1.0-2.0, P = 0.026), principally because of increased triglyceride (TG) levels. The rs1801725 variant allele was associated with a decreased probability of dyslipidemia characterized by non-HDL-cholesterol ≥130 mg/dL and TG ≥200 mg/dL (OR 0.6, 0.4-0.9, P = 0.012). There were no epistatic interactions between CASR and RXRA, LXRA, and ENHO regarding dyslipidemia. Both rs7652589 and rs1801725 SNPs were not in linkage disequilibrium (D' = 0.091, r 2  = 0.003 for the entire HD group) and their haplotypes did not correlate with dyslipidemia. Relative CASR transcript was lower at a borderline significance level in patients harboring the rs1801725 variant allele compared with homozygotes of the major allele (0.20, 0.06-7.80 vs. 0.43, 0.04-5.06, P = 0.058). CASR transcript correlated positively with RXRA transcript (adjusted P = 0.001), LXRA transcript (adjusted P = 0.0009), ENHO transcript (borderline significance, adjusted P = 0.055), dry body weight (adjusted P = 0.035), and renal replacement therapy duration (adjusted P = 0.013)., Conclusions: CASR polymorphisms (rs7652589, rs1801725) are associated with dyslipidemia in HD patients. CASR correlates with RXRA, LXRA, and ENHO at the transcript level. Further investigations may elucidate whether other CASR SNPs contribute to associations shown in this study.

Purpose: Hypospadias is a common developmental anomaly of the male external genitalia. In previous studies conducted on West European, Californian, and Han Chinese populations the relationship between polymorphic variants of the diacylglycerol kinase kappa (DGKK) gene and hypospadias have been reported. The aim was to study the possible associations between polymorphic variants of the DGKK gene and hypospadias using an independent sample of the Polish population., Materials and Methods: Ten single nucleotide polymorphisms in DGKK, which were reported to have an impact on the risk of hypospadias in other populations, were genotyped using high-resolution melting curve analysis in a group of 166 boys with isolated anterior (66%) and middle (34%) forms of hypospadias and 285 properly matched controls without congenital anomalies., Results: Two DGKK variants rs11091748 and rs12171755 were associated with increased risk of hypospadias in the Polish population. These results were statistically significant, even after applying the Bonferroni correction for multiple comparisons (P < .005). All the tested nucleotide variants were involved in haplotype combinations associated with hypospadias. The global p-values for haplotypes comprising of rs4143304-rs11091748, rs11091748-rs17328236, rs1934179-rs4554617, rs1934183-rs1934179-rs4554617 and rs12171755-rs1934183-rs1934179-rs4554617 were statistically significant, even after the permutation test correction., Conclusion: Our study provides strong evidence of an association between DGKK nucleotide variants, haplotypes and hypospadias susceptibility.

Objectives: Genome-wide association studies in patients with endometriosis revealed ten significant single nucleo-tide polymorphisms (SNPs) in the Caucasian population, which include rs12700667 near NFE2L3, rs12037376 in WNT4, rs7521902 near WNT4, rs13394619 in GREB1, rs10859871 near VEZT, rs1537377 near CDKN2B-AS1, rs4141819 near ETAA1, rs7739264 near ID4, rs1519761 near RND3 and rs6542095 near IL1A., Material and Methods: We replicated ten polymorphisms among infertile women with endometriosis (n = 315) and healthy fertile women (n = 406) in the Polish Caucasian population. Genotyping was conducted either by high-resolution melting curve analysis or by a pre-designed TaqMan probe., Results: For all infertile women with endometriosis, the p values of the Cochran-Armitage trend test for the rs12700667 SNP was ptrend = 0.038 and the odds ratio (OR) for the risk allele frequency (RAF) of rs12700667 was 1.304 (95% CI = 1.009-1.685; p = 0.042). In patients with endometriosis with severity stages III/IV, ptrend for rs12700667 SNP was 0.036 and OR for the RAF was 1.394 (95% CI = 1.010-1.923; p = 0.043). In infertile women with endometriosis with severity stages III/IV for rs4141819 SNP, we observed ptrend = 0.026 and for RAF the OR = 1.350 (95% CI = 1.032-1.766; p = 0.029)., Conclusions: Our results demonstrate association of RAF of rs12700667 and rs4141819 SNPs with infertility in Polish women with advanced endometriosis.

Background: The locus on chromosome 15q13.3 containing GREM1 is correlated with the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The aim of the present study was to find the GREM1 functional variants implicated in the aetiology of this common developmental anomaly in the Polish population., Methods: Eight polymorphisms were genotyped in 334 NSCL/P patients and 955 controls. In addition, the GREM1 protein-coding region was sequenced in 96 NSCL/P patients., Results: Significant association with a risk of oral clefts was found for 5 tested polymorphisms. The lowest p(trend) values were identified for rs16969681, rs16969816, and rs1258763 (p(trend) 4.09E-05, 3.35E-05, and 0.0002, respectively). The putative functional variant rs16969681, located in a region that has enhancer activity, was associated with a 2.6-fold lower risk for NSCL/P (odds ratio [OR] = 0.38; 95% confidence interval [CI], 0.24-0.61, p = 2.37E-05). The previously reported association of rs1258763 with NSCL/P was replicated (OR = 0.57; 95% CI, 0.44-0.73; p = 1.10E-05). For all tested GREM1 variants, no significant sex-by-genotype interaction effects were observed. The sequencing analysis did not detect any rare variants implicated in the development of oral clefts., Conclusion: Our results might suggest that variants influencing GREM1 expression levels, rather than variants affecting the function of the encoded protein, are significant factors in NSCL/P etiology., (© 2015 Wiley Periodicals, Inc.)

We investigated the previously-demonstrated association of seven genome-wide association studies (GWAS) single nucleotide polymorphisms (SNPs), including rs2072590 (HOXD-AS1), rs2665390 (TIPARP), rs10088218 and rs10098821 (8q24), rs3814113 (9p22), rs9303542 (SKAP1) and rs2363956 (ANKLE1), as risk factors of epithelial ovarian tumors (EOTs). These SNPs were genotyped in two hundred seventy three patients with EOTs and four hundred sixty four unrelated healthy females from the Polish population. We observed the lowest p values of the trend test for the 9p22 rs3814113 and 8q24 rs10098821 SNPs in patients with all subtypes of ovarian cancer (p(trend) = 0.010 and p(trend) = 0.014, respectively). There were also significant p values for the trend of the 9p22 rs3814113 and the 8q24 rs10098821 SNPs for serous histological subtypes of ovarian cancer (p(trend) = 0.006, p(trend) = 0.033, respectively). Moreover, stratification of the patients based on their histological type of cancer demonstrated, in the dominant hereditary model, a significant association of the 9p22 rs3814113 SNP with serous ovarian carcinoma OR = 0.532 (95% CI = 0.342 - 0.827, p = 0.005, p(corr) = 0.035). Despite the relatively small sample size of cases and controls, our studies confirmed some of the previously-demonstrated GWAS SNPs as genetic risk factors for EOTs.

Introduction: We evaluate whether angiotensinogen AGT M235T (rs699), angiotensin-converting enzyme ACE (I/D) (rs4646994) and aldosterone synthase CYP11B2 -344C/T (rs1799998) polymorphisms can be genetic risk factors of chronic glomerulonephritis (GN) in the Polish population., Materials and Methods: The study was conducted in 140 patients with primary chronic GN: mesangial proliferative GN (MesPGN) (n = 49), IgA nephropathy (IgAN) (n = 31), membranous nephropathy (MN) (n = 27), focal segmental glomerulosclerosis (FSGS) (n = 25), membranoproliferative GN (MPGN) (n = 4), and minimal change disease (MCD) (n = 4), and controls (n = 187). Genotypes were determined by HRM curve analysis for AGT M235T, by PCR and agarose gel separation for ACE (I/D), and by PCR-RFLP for CYP11B2 -344C/T., Results: We found a significant association of the CYP11B2 -344C/T polymorphism in the recessive model with all subtypes of GN (OR = 1.925 (95% CI = 1.152-3.219, p = 0.0118, p(corr) = 0.0354)). We also observed that the CYP11B2 -344C/T polymorphism in the recessive model may also be an independent significant risk factor of IgAN (OR = 2.743 (95% CI = 1.219-6.172, p = 0.0122, p(corr) = 0.0366)), FSGS (OR = 2.895 (95% CI = 1.200-6.985, p = 0.0145, p(corr) = 0.0435)), and all proliferative GNs (MesPGN, IgAN, MPGN) (OR = 2.171 (95% CI = 1.211-3.894, p = 0.0084, p(corr) = 0.0252))., Conclusion: Our results suggest that the CYP11B2 -344C/T polymorphism might be an independent risk factor of IgAN, FSGS and all proliferative chronic GNs., (© The Author(s) 2013.)

Background: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common structural malformation with a complex and multifactorial aetiology. Associations of abnormalities in phenylalanine metabolism and orofacial clefts have been suggested., Methods: Eight single nucleotide polymorphisms (SNPs) of genes encoding phenylalanine hydroxylase (PAH) and large neutral l-amino acid transporter type 1 (LAT1), as well as the PAH mutation that is most common in the Polish population (rs5030858; R408W), were investigated in 263 patients with NSCL/P and 270 matched controls using high resolution melting curve analysis (HRM)., Results: We found that two polymorphic variants of PAH appear to be risk factors for NSCL/P. The odds ratio (OR) for individuals with the rs7485331 A allele (AC or AA) compared to CC homozygotes was 0.616 (95% confidence interval [CI]=0.437-0.868; p=0.005) and this association remains statistically significant after multiple testing correction. The PAH rs12425434, previously associated with schizophrenia, was borderline associated with orofacial clefts. Moreover, haplotype analysis of polymorphisms in the PAH gene revealed a 4-marker combination that was significantly associated with NSCL/P. The global p-value for a haplotype comprised of SNPs rs74385331, rs12425434, rs1722392, and the mutation rs5030858 was 0.032, but this association did not survive multiple testing correction., Conclusion: This study suggests the involvement of the PAH gene in the aetiology of NSCL/P in the tested population. Further replication will be required in separate cohorts to confirm the consistency of the observed association., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms were evaluated as possibly associated with end-stage renal disease (ESRD) resulting from type 2 diabetes mellitus (DM) nephropathy., Methods: Studies were conducted among hemodialysis (HD) patients with ESRD due to type 2 DM nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial nephritis, and hypertensive nephropathy as well as in healthy subjects. A frequency distribution of T-cell-related interleukin (IL) genes (IL18 rs360719, IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917, IL28B, and rs12979860) and vitamin D pathway genes (GC genes: rs2298849, rs7041, and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909, rs10881578, and rs749759) was compared between groups., Results: No significant differences in a frequency distribution of tested polymorphisms were shown between type 2 DM nephropathy patients and controls. A difference was found in IL18 rs360719 polymorphic distribution between the former group and chronic infective tubulointerstitial nephritic patients (P trend = 0.033), which also differed in this polymorphism from controls (P trend = 0.005)., Conclusion: T-cell cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably associated with the pathogenesis of chronic infective tubulointerstitial nephritis.

Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT-related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single-marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non-syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis., (© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Studies have demonstrated that changes in DNA methylation of cancer related genes can be an elementary process accounting for ovarian tumorigenesis. Therefore, we evaluated the possible association of single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) genes, including DNMT1, DNMT3B, and DNMT3A, with ovarian cancer development in the Polish population. Using PCR-RFLP and HRM analyses, we studied the prevalence of the DNMT1 rs8101626, rs2228611 and rs759920, DNMT3A rs2289195, 7590760, rs13401241, rs749131 and rs1550117, and DNMT3B rs1569686, rs2424913 and rs2424932 SNPs in patients with ovarian cancer (n=159) and controls (n=180). The lowest p values of the trend test were observed for the DNMT1 rs2228611 and rs759920 SNPs in patients with ovarian cancer (p trend=0.0118 and p trend=0.0173, respectively). Moreover, we observed, in the recessive inheritance model, that the DNMT1 rs2228611 and rs759920 SNPs are associated with an increased risk of ovarian cancer development [OR 1.836 (1.143-2.949), p=0.0114, p corr=0.0342, and OR 1.932 (1.185-3.152), p=0.0078, p cor=0.0234, respectively]. However, none of other nine studied SNPs displayed significant contribution to the development of ovarian cancer. Furthermore, haplotype and multifactor dimensionality reduction analysis of the studied DNMT1, DNMT3B, and DNMT3A polymorphisms did not reveal either SNP combinations or gene interactions to be associated with the risk of ovarian cancer development. Our results may suggest that DNMT1 variants may be risk factors of ovarian cancer.

Background: The role of vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) in ovarian cancer has been studied in various populations; however, these results are discordant between different ethnicities., Method: Using the polymerase chain reaction-restriction fragment length polymorphism method, we studied the prevalence of the VDR FokI (rs2228570) and BsmI (rs1544410) SNPs in women with ovarian cancer (n=168) and controls (n=182) in a Polish population., Results: We found a significant contribution of the BsmI SNP Bb+BB-versus-bb dominant inheritance model to ovarian cancer development (p=0.0221, p(corr)=0.0442, odds ratio [OR]=1.648 [95% confidence intervals, CI=1.073-2.532]). However, we did not observe an association of the BsmI SNP BB versus Bb+bb recessive inheritance model in patients (p=0.8059, OR=1.093 [95% CI=0.538-2.218]). Moreover, there was no association of FokI SNPs either in Ff+ff versus FF dominant or ff versus Ff+FF recessive inheritance models with ovarian cancer development (p=0.9924, OR=1.002 [95% CI=0.628-1.599] and p=0.1123, OR=1.542 [95% CI=0.901-2.638], respectively). The p-values of the trend test observed for the VDR BsmI and FokI SNPs in patients with ovarian cancer were p(trend)=0.0613 and p(trend)=0.3655, respectively., Conclusion: Our study indicates that the VDR B gene variant might be a moderate risk factor of ovarian cancer development in the Polish population.

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital anomalies, with a complex and still not fully understood etiology. Given the important role of the Wnt/β-catenin pathway during craniofacial development, we decided to test the hypothesis that common polymorphic variants of the genes encoding crucial components of this signaling pathway might contribute to the risk of NSCL/P in the Polish population., Methods: A set of 19 single nucleotide polymorphisms (SNPs) in the APC, AXIN1, AXIN2, CTNNB1, DVL2, and GSK-3β genes were analyzed using restriction fragment length polymorphism and high-resolution melting curve methods in a group of 280 patients with NSCL/P and a properly matched control group (n = 330)., Results: Both single-marker and haplotype analyses showed an association between SNPs in the DVL2 gene and the risk for NSCL/P. The strongest association was found under an overdominant model for the rs35594616 variant located in the exonic sequence of DVL2 (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.37-2.62; p < 0.0001). Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction between DVL2 gene SNPs in the susceptibility to orofacial clefts. Borderline association with a decreased risk of NSCL/P was also observed for the AXIN2 rs3923087 variant (dominant model OR, 0.69; 95% CI, 0.50-0.95; p = 0.03)., Conclusion: This study suggests that polymorphic variants of the Wnt/β-catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The interleukin (IL)18 rs360719 CC genotype is associated with the development of antibodies to hepatitis B virus surface antigen (anti-HBs) in hemodialysis (HD) patients. IL18 shares biological properties with IL12 in promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the IL12A 3` untranslated region (UTR) and IL12B 3`UTR may contribute to anti-HBs development (titre ≥ 10 IU/L) in HD patients either individually or jointly with the IL18 polymorphism., Methods: In 518 HD patients and 240 controls the IL12A rs568408 3'UTR G > A polymorphism was genotyped by high-resolution melting curve analysis. Polymerase chain reaction restriction fragment length polymorphism was used to detect the IL12B rs3212227 3'UTR A > C and IL18 -1297 T > C rs360719 polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and the risk of impaired anti-HBs development were estimated by computing the odds ratios and their 95% confidence intervals using logistic regression analysis., Results: In the logistic regression analysis, the higher frequency of rs360719 CC individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311 patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or rs3212227 AA (p = 0.046) was associated with an increased chance for the development of anti-HBs in HD patients. Patients bearing both rs568408 AA and rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop anti-HBs compared with those carrying any other genotype (p = 0.005) or those who had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development than carriers of any other genotype (p = 0.042)., Conclusion: Development of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.

Various studies have indicated that chemokines such as monocyte chemotactic protein-1 (MCP-1) play an important role in the pathogenesis of primary glomerulonephritis (GN) and other glomerular diseases. Moreover, patients with primary GN display aberrant galactosylation of the O-linked carbohydrate moieties of IgA. Therefore, we analysed the distribution of the functional MCP-1 -2518 A > G (rs 1024611) and 1 beta 1,3-galactosyltransferase (C1GalT1) 1365 A > G (rs1047763) polymorphic variants in patients with primary GN (n = 144) and controls (n = 437) in a sample of the Polish population. We did not find a significant difference in the prevalence of the MCP-1 -2518 A > G and C1GalT1 1365 A > G polymorphisms in patients with primary GN and healthy individuals. Odds Ratio (OR) for GN patients with the MCP-1 -2518 GG genotype was 0.869 (95% CI = 0.410-1.840, P = 0.7130), and OR of the -2518 GG and -2518AG genotypes was 1.004 (95% CI = 0.689-1.464, P = 0.9836). OR for C1GalT1 1365AA genotype was 0.484 (95% CI = 0.181-1.293, P = 0.1402) and OR of the 1365AA and 1365AG genotypes was 0.839 (95% CI = 0.573-1.228, P = 0.3651). We also did not observe a difference in the distribution of alleles between patients and controls. The MCP-1 -2518 G allelic OR was 0.976 (95% CI = 0.725-1.314, P = 0.8744). The OR for the C1GalT1 1365A allele was 0.816 (95% CI = 0.596-1.118, P = 0.205). Moreover, there was no significant association between the MCP-1 -2518 A > G and C1GalT1 1365 A > G genotypes with different morphological types of primary GN or clinical manifestations. Our observations indicate that the MCP-1 -2518 A > G and C1GalT1 1365 A > G polymorphisms might not be a risk factor in the incidence of primary GN in the Polish population.

Data indicates that genetic factors alone do not account for ovarian tumorigenesis, suggesting that epigenetic status additionally affects this process. Therefore, we assessed the possible contribution of polymorphic variants of genes that may affect DNA methylation to the risk of ovarian cancer incidence in the Polish population. Using PCR-RFLP and HRM analyses, we studied the distribution of BHMT (rs3733890), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394) and TCN2 (rs1801198) genotypes and alleles in patients with ovarian cancer (n = 136) and controls (n = 160). Moreover, using DNA and methylation-specific PCR (MSP) we also determined the methylation of the Cadherin 13 (CDH13) promoter in cancerous tissue from these patients. We did not observe a significant association between all studied gene variants and the incidence of ovarian cancer. The lowest P (trend) = 0.1226 was observed for the MTHFR Ala222Val polymorphism. Moreover, the lowest P = 0.0772 was found in the comparison of MTHFR Ala/Ala versus Val/Val and Val/Ala genotypes in patients and control groups. The multifactor dimensionality reduction analysis also did not indicate a significant interactive genetic effect on ovarian cancer incidence for all analyzed SNPs. However, we observed frequent methylation of the CDH13 promoter in approximately 21% (29/136) patients with ovarian carcinomas. Our results might suggest that the selected polymorphic gene variants may not contribute to ovarian cancer incidence.

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size.

Background: Non-syndromic cleft lip and palate (CLP) is one of the most common birth defects. Recent genome-wide association studies (GWAS) have identified several novel risk loci associated with this craniofacial anomaly. Therefore, the objective of this report was to investigate the contribution of the top seven polymorphisms reaching genome-wide statistical significance in GWAS analyses in the Polish population., Methods and Results: Nucleotide variants located at chromosomal regions 1p22.1, 10q25.3, 17q22, and 20q12 were tested in a group of 206 patients with nonsyndromic CLP and a properly matched control group. Significant results, which persisted even after Bonferroni correction (p < 0.0071), were observed for polymorphisms located at 10q25.3 (rs7078160 and rs4752028) and 17q22 (rs227731). Under a recessive model, both rs7078160 and rs4752028 were associated with a greater than fourfold increase in the risk of CLP (odds ratio [OR] = 4.536; 95% confidence interval [CI], 1.678-12.265; p = 0.0012 and OR = 4.573; 95% CI, 1.817-11.512; p = 0.0004, respectively). Polymorphism rs227731 increased the risk of CLP when analyzed under a dominant model (OR = 1.732; 95% CI, 0.184-2.253; p = 0.0044). Borderline association was alsoidentified for the 1p22.1 locus (rs481931). Moreover, 10q25.3 haplotypes were significantly associated with a susceptibility to CLP., Conclusion: Our evaluation study confirmed a substantial association of polymorphisms located at chromosomal regions 10q25.3 and 17q22 with nonsyndromic CLP in the Polish population., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: Endometriosis has been considered an epigenetic disease. Single nucleotide polymorphisms (SNPs) located in genes encoding enzymes of the folate and choline metabolism may affect DNA methyltransferase activity., Study Design: We studied 16 SNPs in 12 folate and choline metabolism genes, including BHMT (rs7356530 and rs3733890), BHMT2 (rs625879), CBS (844ins68), CHDH (rs893363 and rs2289205), CHKA (rs7928739), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394), PCYT1A (rs712012 and rs7639752), PEMT (rs4244593 and rs4646406) and TCN (rs1801198) in one hundred and sixty-three infertile women with minimal endometriosis and one hundred and fifty fertile women., Results: There were no significant differences between genotype and allele frequencies of these gene variants in infertile women with endometriosis (n=163) and controls (n=150). The lowest, but not statistically significant, p values of the trend test were observed for the CBS 844ins68 and MTR rs1805087 (ptrend=0.0527 and ptrend=0.0771, respectively) polymorphisms. However, the exhaustive multifactor dimensionality reduction analysis revealed an epistatic interaction between rs1801133 of MTHFR and rs4244593 of PEMT in endometriosis-associated infertility (p=0.0240)., Conclusions: Our results showed moderate evidence for the contribution of SNPs located in genes encoding folate and choline metabolism enzymes to infertility in women with endometriosis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population., Methods: We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group., Results: Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR](AG+AAvsGG), 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382-2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025)., Conclusions: Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample., (2010 Wiley-Liss, Inc.)

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism 677C>T has been shown to be a risk factor for psychiatric disorders. We investigated the genotype and allelic frequencies of MTHFR 677C>T polymorphism in the group of patients with bipolar disorder type I (BDI) (n=200) and schizophrenia (n=200), and in the control group (n=300). Odds ratio (OR) for patients with BD and schizophrenia with 677T allele was 1.988 ((95% CI=1.370-2.883); P=0.0003 (P=0.0006 after Bonferroni correction)) and 1.796 ((95% CI=1.237-2.609); P=0.0020 (P=0.0040 after Bonferroni correction)), respectively. The stratification of patients based on gender revealed significant association of 677T allele with male patients with BDI and schizophrenia (OR=2.393; 95% CI=1.429-4.006; P=0.0008 and OR=2.036; 95% CI=1.207-3.433; P=0.0073, respectively). This finding indicates possible association of BD and schizophrenia with the 1p36.3 MTHFR locus.

The aetiology of non-syndromic cleft lip with or without cleft palate (CL/P) is very complex. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors of having a child with this craniofacial anomaly. Therefore, in our study, mothers with CL/P children as well as control mothers were examined for prevalence of polymorphisms of genes that encode methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1). We observed that there were no statistical differences in allele and genotype frequencies of MTHFR c.677C>T, MTHFD1 c.1958G>A and RFC1 c.80G>A between mothers who had children with CL/P and control mothers. However, mothers with MTR c.2756AG or GG genotype displayed a 2.195-fold increased risk of having a child with CL/P (95% CI 1.189-4.050, p = 0.011). The mechanism by which polymorphic transition of MTR gene might increase the maternal risk of having CL/P progeny is unknown. Our observations are consistent with a significant role of the methyl cycle in the development of craniofacial structures in humans.

PAX9 is a paired domain transcription factor that plays a critical role in odontogenesis. All mutations of PAX9 identified to date have been associated with nonsyndromic form of tooth agenesis. The present report describes an unusual novel mutation in PAX9 identified in a family with severe molar oligodontia. This heterozygous deletion combined with 24 bp insertion (including a 5' splice site) is localized in the second exon beyond the highly conserved paired box sequence, and might result either in a premature termination of translation at aa 210 or in an aberrant splicing, leading to a frameshift and premature termination of translation at aa 314. Real-time PCR analysis revealed no mutated transcript in cultured lymphocytes of one of the affected individuals indicating that the novel mutation might result in rapid degradation of the mutated transcript leading to haploinsufficiency of PAX9. Our results support the view that mutations in PAX9 constitute a causative factor in nonsyndromic oligodontia.