A functional variant of miRNA‐149 confers risk for allergic rhinitis and comorbid asthma in Chinese children

The prevalence of allergic rhinitis (AR) and asthma has been increasing, and the comorbidity rates of these diseases are very high. Here, 176 AR patients, 124 patients with comorbid AR and asthma (AR‐A) and 206 healthy Chinese children as controls were included in a case–control study. Six single‐nucleotide polymorphisms (SNPs), miR‐146a (rs2910164, rs57095329 and rs6864584), miR‐196a2 (rs11614913), miR‐499 (rs3746444) and miR‐149 (rs2292832), were genotyped. The prevalence of homozygous miR‐149 (rs2292832) CC genotype and C allele were considerably increased in AR and AR‐A patients, compared with the controls. AR‐A group showed higher frequencies of CC genotype and C allele of rs2292832 than AR group. No significant difference in the genotypic and allelic frequencies of other miRNA SNPs was found between the groups. MiR‐149 levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in CC (variant type) cases compared with TT (wild‐type) cases. In further experiments, PBMCs obtained from the healthy controls with CC, CT and TT genotypes were stimulated by house dust mite extracts, which led to a significant decrease in the levels of miR‐149 in PBMCs obtained from CC and TT individuals. This decrease was more pronounced in CC compared with TT cases. Our results demonstrate that miR‐149 rs2292832 variant is not only strongly associated with AR and AR‐A, but it may lead to an increase in the susceptibility to allergies following the stimulation with an allergen, through the changes in miR149 expression. Additionally, AR patients with CC genotypes were shown to be more susceptible to asthma.     

Methylenetetrahydrofolate Reductase C667T Polymorphism is Associated with Increased Risk of Coronary Artery Disease in a Chinese Population

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)‐2, tumour necrosis factor (TNF)‐α, macrophage migration inhibitory factor (MIF) rs755622 G/C and cyclin D1 (CCND1) rs678653 G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix‐assisted laser desorption ionization/time‐of‐flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP‐2 rs243865 C/T, TNF‐α rs1800629 A/G, MIF rs755622 G/C and CCND1 rs678653 G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings.     

A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression

The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3′‐untranslated region (3′‐UTR) of the gene via interactions with microRNAs. Using a series of in silico assays, we selected the candidate microRNAs (miRNAs) with the potential to interact with functional SNPs of TAP2. The SNP rs241456—located in the 3′‐UTR of TAP2—resides in a potential binding site for hsa‐miR‐1270 and hsa‐miR‐620. HEK 293 cells, from a human kidney cell line, were used to characterize the extent of binding of miRNAs to each polymorphic allele of the SNP by a luciferase reporter gene assay. RNA electrophoretic mobility shift assays were used to evaluate the interaction between the miRNAs and each allele sequence of the SNP. We found that hsa‐miR‐1270 inhibited luciferase activity by binding to the T allele of the SNP in an allele‐specific manner. A negative correlation was also found between the expression of hsa‐miR‐1270 and the T allele of the SNP in kidney tissues. Our findings support the hypothesis that hsa‐miR‐1270 suppresses the production of TAP2 by binding to this SNP in the 3′‐UTR of this gene. Environ. Mol. Mutagen. 59:134–143, 2018. © 2017 Wiley Periodicals, Inc.     

Association of interleukin‐16 polymorphisms with disease progression and susceptibility in endometriosis

Interleukin‐16 (IL‐16) is a multifunctional pro‐inflammatory cytokine that was previously found in association with complex disorders, and it is now cleared that this cytokine plays a critical role in regulation of cellular functions such as homoeostasis. Due to the complexity of endometriosis and its resemblance to cancer, we designed present case–control study to determine the effects of genetic polymorphisms of the human IL‐16 gene on Iranian women's susceptibility to endometriosis. A total of 126 patients with endometriosis (stages I–IV) and 144 healthy women as control group were recruited to the study. We genotyped four single nucleotide polymorphisms of IL‐16 gene (rs11556218 T>G, rs4778889 T>C, rs4072111 C>T and rs1131445 C>T). Genotyping was performed using PCR and restriction fragment length polymorphism. Our results showed that genotype distribution in two exonic polymorphisms including rs11556218 and rs4072111 was significantly different between Endometriosis patients and healthy individuals (P < 0.05). We have also found an association between rs4072111 and rs1131445 with progression to the severe stages (III–IV) of endometriosis (P < 0.05). Finally, we may conclude that IL‐16 gene polymorphisms are highly associated with increased risk of endometriosis and could be considered as a susceptibility factor for endometriosis.     

Association of Interleukin‐1 beta and tumor necrosis factor‐alpha genetic polymorphisms with gastric cancer in India

Interleukin 1 beta (IL‐1β) and Tumor necrosis factor alpha (TNF‐α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL‐1β and TNF‐α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL‐1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30‐2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67‐3.83) and TNF‐α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54‐3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 “effective” risk alleles conferred a risk of almost 10‐fold in comparison to individuals carrying less than 3 “effective” risk alleles. Our survival analysis also indicated a significant association between IL‐1β rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL‐1β rs1143627:CC and rs16944:TT genotypes. Further, meta‐analysis revealed significant association of IL‐1β rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18‐14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48‐20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653–667, 2018. © 2018 Wiley Periodicals, Inc.     

Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort

Single‐nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR‐146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR‐146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age‐ and gender‐matched healthy controls using T‐ARMS‐PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ² = 63.10; P = <0.0001) and allelic frequencies (OR = 0.3955 (0.3132–0.4993); P = < 0.0001) was observed between cases and controls. Furthermore, we also found that miR‐146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR = 0.2397 (0.1629–0.3526); P = 0.0001; GG vs. GC + CC) and recessive (OR = 2.803 (1.865–4.213); P = <0.0001; CC vs. GC + GG) inheritance models. In summary, miR‐146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.     

Association between the interleukin-1B polymorphism at rs16944 T>C and diabetic retinopathy

Diabetic retinopathy (DR) is a common microvascular complication of diabetes and the leading cause of blindness at working age. DR is considered to be a chronic low-grade inflammatory subclinical disease, and its pathogenesis is related to genetic and environmental factors. Interleukin (IL)-1 is an important inflammatory cytokine. An association between DR and the rs16944 (IL-1B-511) T>C gene polymorphism has not been reported. The aim of this study was to investigate the association between the rs16944 T>C gene polymorphism and DR in the Han population in southwest China. Participants in this study were 272 patients with DR, 274 patients with type 2 diabetes mellitus (T2DM), and 335 healthy controls (NC). The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the rs16944 T>C genotype of participants. The distribution frequencies of the rs16944 T>C genotype and allele were significantly different among the three groups (p < .05). The distribution frequency of TT, CT, CC genotype (χ² = 9.893, p = .007; χ² = 6.567, p = .037) and each allele (χ² = 5.585, p = .018; χ² = 9.187, p = .002) in the DR group was significantly different from the NC and T2DM groups, respectively. Logistic regression analysis showed that the TT + CT genotype was a risk factor for DR, with an odds ratio of 1.731 (95% confidence interval 1.140–2.627, p = .01). The rs16944 T>C gene polymorphism may be associated with DR, and the TT+CT genotype may increase the risk of DR.     

The Impact of FOXP3 Polymorphism on the Risk of Allergic Rhinitis: A Meta‐Analysis

Polymorphisms of several genes were reported to be associated with the risk of allergic rhinitis. Here, we first conducted a meta‐analysis to evaluate the potential genetic association between the polymorphisms of the FOXP3 (Forkhead Box P3) gene and the susceptibility to allergic rhinitis. A total of 2671 relevant articles were initially retrieved from the databases of PubMed, Web of Science, Embase, WANFANG/CNKI and Scopus, and six eligible case‐control studies were finally enrolled in our meta‐analysis, according to our strict inclusion/exclusion criteria. Based on the extracted data, Mantel–Haenszel statistic, Cochrane's Q statistic, I² test, subgroup meta‐analysis, Begg's test, Egger's test and sensitivity analysis were performed via Stata/SE 12.0 software. The results of the Mantel–Haenszel statistic regarding rs3761548 showed that no significant difference was observed in the allergic rhinitis case and population‐based control group under the genetic models of A versus C, AA versus CC, CA+AA versus CC, AA versus CC+CA and carrier A versus C (all P‐value of Association Test, P_A > 0.05), apart from CA versus CC (P_A = 0.020). The similar results were obtained in the subgroup analysis of Asian. In addition, we did not obtain the positive result in the meta‐analysis of rs2232365 (all P_A > 0.05). We also excluded the presence of large publication bias through Begg's test and Egger's test, and we confirmed the stability of data by sensitivity analysis. In summary, no significant association between rs3761548, rs2232365 polymorphisms of the FOXP3 gene, and an increased susceptibility to allergic rhinitis was identified based on the published data; however, this conclusion should be confirmed by more studies with increased sample sizes.     

FcεRIα gene (FCER1A) promoter polymorphisms and total serum IgE levels in Japanese atopic dermatitis patients

Two promoter polymorphisms of the high-affinity IgE receptor α-subunit (FcεRIα) gene (FCER1A), −66T>C (rs2251746) and −315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the −315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of −315CT/TT genotype or the −315T allele was significantly higher in those with highly elevated total serum IgE concentrations.     

Functional variant in microRNA‐196a2 contributes to the susceptibility of congenital heart disease in a Chinese population

Hox gene clusters play an important role during cardiac septation to valve formation in different species, and the miR‐196a‐HOXB8‐Sonic hedgehog signaling pathway is of particular interest. Recently, we found that a genetic variant of rs11614913 in the miR‐196a2 sequence could alter mature miR‐196a expression and target mRNA binding; this observation led us to hypothesize that rs11614913 might influence susceptibility to sporadic congenital heart disease (CHD). We conducted a three‐stage case–control study of CHD in Chinese to test our hypothesis by genotyping miR‐196a2 rs11614913 and three other pre‐miRNA SNPs (miR‐146a rs2910164, miR‐149 rs2292832, and miR‐499 rs3746444) in 1,324 CHD cases and 1,783 non‐CHD controls. We found that rs11614913 CC was associated with a significantly increased risk of CHD in all three stages combined (P=6.81×10^?6). In a genotype–phenotype correlation analysis using 29 cardiac tissue samples of CHD, rs11614913 CC was associated with significantly increased mature miR‐196a expression (P=0.001). In vitro binding assays further revealed that the rs11614913 variant affects HOXB8 binding to mature miR‐196a. This is the first study to indicate that miR‐196a2 rs11614913 plays a role in sporadic CHD susceptibility. Hum Mutat 30:1–6, 2009. © 2009 Wiley‐Liss, Inc.     

ORIGINAL ARTICLE: Transforming Growth Factor‐Beta1 Gene Polymorphisms in Korean Patients with Pre‐eclampsia

Citation Kim SY, Lim JH, Park SY, Yang JH, Kim MY, Kim MH, Ryu HM. Transforming growth factor‐beta1 (TGF‐β1) gene polymorphisms in Korean patients with pre‐eclampsia. Am J Reprod Immunol 2010; 63: 291–298 Problem The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor‐beta1 (TGF‐β1) gene are associated with development of pre‐eclampsia (PE) in Korean women. Method of study We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing. Results The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR‐complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR‐complicated PE compared with the 869TT genotype. The TGF‐β1 c.915G>C polymorphism was not detected in our population. Conclusion Our findings indicate that the TGF‐β1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR‐complicated PE.     

Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

Our aim was to evaluate the association of genetic polymorphisms of immunoregulatory molecules with susceptibility to hepatocellular carcinoma (HCC). The polymorphisms in CTLA‐4 (?318 T/C, CT60 G/A), TNF (?238 G/A, ?308 G/A) and IL10 (?592 C/A, ?819 C/T) were genotyped by PCR and DNA sequencing. The functional relevance of the polymorphisms was examined by ELISAs, in vitro lymphocyte proliferation assay and cytotoxic assay. The CTLA‐4 ?318 TC/TT, CTLA‐4 CT60 GG, IL10 ?592 CA and ?819 CT/TT variants, CTLA‐4 ?318 T and IL 10 ?819 T alleles were positively associated with HCC risk (P < .05). While TNF ?238 AA variant, TNF ?238 A allele were associated with decreased risk of HCC (P < .05). Furthermore, combinations of CTLA‐4 ?318 TC/TT and TNF ?238 GG/GA; CTLA‐4 ?318 TC/TT and IL 10 ?819 CC; CTLA‐4 ?318 CC and IL 10 ?819 CT/TT in patients with HCC were statistically significant (P < .05). Peripheral blood mononuclear cells (PBMCs) carrying ?318 TC/TT genotypes exhibited significantly lower proliferation rates, decreased IL‐2, IL‐4 levels, fewer cytolytic activities and elevated TGF‐β levels. For IL 10 ?819 C/T, the CC genotype was significantly associated with higher proliferation rate, decreased TGF‐β, IL‐10 levels and higher cytolytic activities (P < .05). For TNF ?238 G/A, the AA genotype only had association with serum IL‐2, IL‐4 (P < .05). In addition, we also found that CTLA‐4 ?318 T/C, IL‐10 ?819 T/C variants, combinations of CTLA‐4 ?318 CC with IL 10 ?819 CT or TT, CTLA‐4 ?318 TC or TT with IL 10 ?819 CT or TT were associated with the severity of HCC. These findings suggest that CTLA‐4 ?318 TC/TT and IL 10 ?819 CT/TT could promote the pathogenesis of HCC, which might be related with down‐regulation of Th1/Th2‐type cytokines and/or up‐regulation of Th3‐type cytokines.     

Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI,Blood Hemoglobin,Hypertension, and Cerebrovascular Events,the TAMRISK Study

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase‐2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele‐specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20–I25) and incidence of cerebrovascular diseases (I60–I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low‐density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology.     

Polymorphisms of xenobiotic‐metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan

Cytochrome P450 (CYP), glutathione‐S‐transferase (GST), and N‐acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39–12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51–14.9) were significantly associated with CRC risk when compared to wild‐type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12–0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic‐metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69–78, 2018. © 2017 Wiley Periodicals, Inc.     

A five‐miRNA expression signature predicts survival in hepatocellular carcinoma

The aim of this study was to identify a microRNA (miRNA) expression signature for predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients in The Cancer Genome Atlas (TCGA) database were randomly divided into training and testing set. miRNAs, associated with survival time in the training set, were identified by using univariate Cox regression analysis. The risk score was formulated based on the expression levels of these miRNAs. Then the miRNA signature was validated in testing set through Kaplan–Meier analysis and log‐rank test. hsa‐miR‐301a, hsa‐miR‐132, hsa‐miR‐212, hsa‐miR‐489, and hsa‐miR‐1468 were identified to formulate risk score in training set and used to calculate the risk score of each patients in testing set. About 161 patients in testing set were segregated into high‐ and low‐risk group according to the median risk score. The survival time of high‐risk group was significantly shorter (p = 0.0248) than low‐risk group in testing test. The target genes of five miRNAs were significantly enriched in valine, leucine, and isoleucine degradation pathway and PPAR signaling pathway. hsa‐miR‐1468 had an up‐regulated tendency in HCC tissues compared to adjacent tumor tissues. The expression of hsa‐miR‐301a, hsa‐miR‐132, hsa‐miR‐212, hsa‐miR‐489, and hsa‐miR‐1468, which might be potential biomarkers to evaluate HCC patients' prognosis.     

Functional SNP in 3′‐UTR MicroRNA‐Binding Site of ZNF350 Confers Risk for Age‐Related Cataract

Many studies have suggested that individual susceptibility to age‐related cataract (ARC) may be associated with DNA sequence polymorphisms affecting gene regulation. As DNA repair is implicated in ARC pathogenesis and single‐nucleotide polymorphisms (SNPs) in the 3′‐terminal untranslated region (3′‐UTR) targeted by microRNAs (miRNAs) can alter the gene function, we hypothesize that the miRNA‐binding SNPs (miRSNPs) in DNA double‐strand break repair (DSBR) and nucleotide excision repair (NER) pathways might associate with ARC risk. We genotyped nine miRSNPs of eight genes in DSBR and NER pathways in Chinese population and found that ZNF350‐ rs2278414:G>A was significantly associated with ARC risk. Even though the Comet assay of cellular DNA damage indicated that all the subtypes of ARC patients had more DNA breaks in peripheral lymphocytes than the controls independent of rs2278414 genotypes, individuals carrying the variant A allele (AA and AG) had lower ZNF350 mRNA levels compared with individuals with GG genotype. Moreover, the in vitro experiment indicated that miR‐21‐3p and miR‐150‐5p specifically downregulated luciferase reporter expression in the cell lines transfected with rs2278414 A allele compared with rs2278414 G. These results suggested that the association of SNP rs2278414 with ARC might involve an altered miRNA regulation of ZNF350.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.