Correlation of TNF-α polymorphisms with susceptibility to lung cancer: evidence from a meta-analysis based on 29 studies.

OBJECTIVE: This meta-analysis aims to clarify the association between the TNF-α -308G > A and - 238G > A polymorphisms and lung cancer risk. METHOD: A comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software. RESULTS: The analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the - 238G > A polymorphism. The - 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the - 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002). CONCLUSION: The - 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the - 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor.

A Comprehensive Compilation of Data on the Relationship Between Surfactant Protein-B (SFTPB) Polymorphisms and Susceptibility to Neonatal Respiratory Distress Syndrome.

BACKGROUND: This study aims to explore the association between variations in the Surfactant Protein-B (SFTPB) gene and the risk of neonatal respiratory distress syndrome (NRDS). METHODS: A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, and CNKI databases up to February 10, 2024, to identify pertinent studies. RESULTS: A total of seventeen studies examining the +1580 C/T polymorphism (2,058 cases and 2,596 controls) and five studies investigating the -18 A/C polymorphism (680 cases and 739 controls) were included in the analysis. The pooled data indicated that the +1580 C/T polymorphism confers a protective effect against NRDS in various populations and ethnic groups. Conversely, the -18 A/C polymorphism did not demonstrate a significant association either globally or among Asian neonates. CONCLUSIONS: The +1580 C/T variant appears to be protective against NRDS, whereas the -18 A/C polymorphism shows minimal impact on the disease's progression.

A Comprehensive Consolidation of Data on the Relationship Between Surfactant Protein-B (SFTPB) Polymorphisms and Susceptibility to Bronchopulmonary Dysplasia.

BACKGROUND: This meta-analysis aims to evaluate the potential link between common variations in the Surfactant Protein-B (SFTPB) gene and the risk of bronchopulmonary dysplasia (BPD) in preterm neonates. METHODS: All pertinent articles published prior to February 1, 2024, in PubMed, Web of Science, EMBASE, CNKI, and Scopus databases were reviewed. RESULTS: Nineteen case-control studies involving 1149 BPD cases and 1845 non-BPD controls, were analyzed. Combined data indicated a significant link between SFTPB -18 A > C and Intron 4 VNTR polymorphisms with increased BPD susceptibility, while the 1580 C > T polymorphism provides a protective impact on BPD initiation. CONCLUSIONS: Pooled data indicated a significant association between SFTPB -18 A > C and Intron 4 VNTR polymorphisms with increased BPD risk, whereas the 1580 C > T polymorphism confers protection. These findings suggest a genetic susceptibility to BPD, underscoring the complex interplay of different genetic elements in its development.

A novel nonsense variant in the ATL3 gene is associated with disturbed pain sensitivity, numbness of distal limbs and muscle weakness.

Introduction Hereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance. Methods We sudied and examined who present with sensory disturbances and muscle weakness in their lower limb. Patients underwent Whole Exome Sequencing and Sanger sequencing was performed in families for validation of detected variant. Results Here, we identified two Iranian families carrying the novel heterozygous stop variant NM_015459.5: c.16C>T, p.Arg6Ter in ATL3 that led to disturbed pain and touch sensitivity. This variant in the ATL3 gene was detected in both families (NM_015459.5: c.16C>T, p.Arg6Ter) by whole-exome sequencing and confirmed by Sanger sequencing. Conclusion In this study, the subjects manifested weakness of distal limb muscles and numbness of the lower extremities. In addition, some unusual features, including hearing problems and inability to sit and walk presented in one of the patients. Eventually, we provide a case-based review of the clinical features associated with HSN1F. Hitherto, only 11 patients with HSN1F have been reported. We compared our findings to previously reported cases, suggesting that the clinical features are generally variable in the HSN1F patients.

Clinical features of patients with Yin Yang 1 deficiency causing Gabriele-de Vries syndrome: A new case and review of the literature.

BACKGROUND: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in YY1. In this study, we report a 10-year-old boy with a de novo novel pathogenic variant in YY1, the first Iranian patient with Gabriele-de Vries Syndrome. METHODS: The novel de novo pathogenic variant detected in this study (NM_003403:c.690delA, p.Glu231Ilefs*25) was identified by whole-exome sequencing and confirmed by Sanger sequencing. RESULTS: The proband presented with delayed motor and speech development, ataxia, abnormal gait, autistic behavior, brain atrophy, and severe learning disability. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries Syndrome. Thus far, merely 13 Gabriele-de Vries Syndrome patients have been reported in the literature. CONCLUSION: The investigations for a suspected case of Gabriele-de Vries Syndrome must involve molecular diagnosis of the disease and its underlying genetic defect because the clinical investigations are generally variable and nonspecific.

Recurrent Infections and Immunodeficiency Caused by Severe Pancytopenia Associated with a Novel Life-Threatening Mutation in Hypoxia-Upregulated Protein 1.

HYOU1 encodes a protein from the endoplasmic reticulum chaperone proteins, expressed to protect cellular mechanisms from stress such as hypoxia, insufficient energy and excessive or insufficient substances, and to restore cell homeostasis. In this study, we report a novel pathogenic variant in HYOU1. The proband, the second patient with pathogenic variant in HYOU1, was a female born to consanguineous parents. A novel homozygous pathogenic variant in HYOU1 (NM_001130991.3: c.1456C>T; p.Arg486Cys) was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age. Both parents are heterozygous for this variant and have no issues related to this study.

Association of +1923C > T, -1112C > T and +2044A > G Polymorphisms in IL-13 Gene with Susceptibility to Pediatric Asthma: A Systematic Review and Meta-Analysis.

BackgroundPrevious studies have provided conflicting evidence implicating the IL-13 polymorphism and pediatric asthma. Thus, we performed a meta-analysis to combine and analyze the available studies to provide more accurate conclusions. Methods: A comprehensive retrieval in PubMed, EMBASE, Web of Science, and CNKI was performed up to February 05, 2020. Results: A total of 39 case-control studies including 15 studies with 4,968 cases and 7,091 controls were on +1923 C > T, ten studies with 3,175 cases and 2,983 controls on -1112 C > T, and 14 studies with 4,476 cases and 5,121 controls on +2044 A > G were selected. Pooled data showed that the IL-13 + 1923 C > T, -1112 C > T and +2044 A > G polymorphisms were significantly associated with risk of pediatric asthma. The IL-13 + 1923 C > T (Asians and Africans), -1112 C > T (Caucasians) and +2044 A > G (Asians) polymorphisms were more frequently associated in these ethnic groups. Conclusions: Our pooled data indicated that IL-13 + 1923 C > T, -1112 C > T and +2044 A > G polymorphisms were correlated with risk of pediatric asthma.

Association of IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms with susceptibility to chronic and aggressive periodontitis: a systematic review and meta-analysis.

OBJECTIVES: Several epidemiological studies have evaluated association of interleukin 10 (IL-10) polymorphisms with risk of periodontitis. However, the results remain conflicting and inconclusive. Here, we carried out a comprehensive systematic review and meta-analysis to evaluate the association of IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms with risk of chronic (CP) and aggressive (CP) periodontitis. METHODS: Electronic databases including PubMed, Science Direct, SciELO, and CNKI were systematically searched to identify all relevant studies published up to 01 June 2020. RESULTS: A total of 60 case-control studies with 5313 cases and 6528 controls met our inclusion criteria. Overall, the pooled data showed that the IL-10 -592C>A polymorphism was statistically associated with increased risk of periodontitis in the overall population, while no significant association was identified for IL-10 -1082A>G and IL-10 -819C>T polymorphisms. The subgroup analysis by ethnicity revealed that the IL-10 -1082A>G polymorphism was significantly associated with periodontitis risk in Caucasians, IL-10 -819C>T polymorphism in mixed population, and IL-10 -592C>A polymorphism in both Asians and mixed populations. When further analyzed by periodontitis type, only the IL-10 -592C>A polymorphism was associated with CP risk, but not AgP; and the IL-10 -1082A>G and -819C>T polymorphisms have not positive association neither in the CP and AgP. CONCLUSIONS: The current meta-analysis showed that the IL-10 -592C>A polymorphism was statistically associated with periodontitis risk in the overall population. Moreover, the IL-10 -1082A>G, IL-10 -819C>T, and IL-10 -592C>A polymorphisms were associated with periodontitis risk by ethnicity. Therefore, the IL-10 polymorphisms are of high clinical relevance by ethnicity and would be a useful marker to identify patients who are at higher risk for periodontitis.

Gender difference in determinant factors of being overweight among the 40-70-year-old population of Kharameh cohort study, Iran.

BACKGROUND: Iranians face being overweight as one of the most common health problems, which is more prevalent among women. This study aimed to identify gender differences in determinants of being overweight in 40- to 70-year-old participants from Kharameh, Iran. METHODS: This cross-sectional study was conducted during 2015-2016. The total 10,663 inhabitants of Kharameh, Iran, aged 40-70 years old, were target population. Those with a body mass index (BMI) < 18.5 or > 29.9 were excluded. A checklist composed of socio-demographic, lifestyle, and BMI items was used; a p-value < 0.05 was considered significant. RESULTS: Overall, 53.4% of 8222 participants were overweight. The prevalence of overweight women (62.7%) was significantly higher (p <  0.001) than men (43.6%). The logistic regression model for men showed that being overweight was more likely among men with cigarette smoking history (OR = 1.49) and those with a moderate physical activity level (OR = 1.35), but less likely among those with a higher socio-economic status (SES) (OR = 0.74). Among women, being overweight was associated with high SES (OR = 1.61), an education level below high school diploma (OR = 1.57) and primary school education (OR = 1.50), being married (OR = 2.39), widowed (OR = 2.11) and having a greater calorie intake (OR = 1.01). Being overweight was less likely among employed women (OR = 0.85), those with cigarette smoking history (OR = 0.65), and those with high (OR = 0.72) and intensive physical activity (OR = 0.73). CONCLUSIONS: This study revealed the gender differences in determining factors affecting being overweight. As being overweight was more prevalent among women, the priority of health policies to control this issue should also be focused on women.

A meta-analysis for association of eNOS VNTR 4b/a, - 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss.

BACKGROUND: The association of polymorphisms at nitric oxide synthases (eNOS) gene with recurrent pregnancy loss (RPL) susceptibility has been the focus of attention in several studies. However, the conclusions have been divergent and controversial. Therefore, we performed this study to precisely evaluate the association of eNOS polymorphisms with the risk of RPL. METHODS: A universal search in PubMed, Web of Knowledge, SciELO, MedRxiv, Scopus and web of Science was performed to identify relevant studies up to January 25, 2020. RESULTS: A total of 39 eligible studies including 15 studies with 2274 cases and 1933 controls on VNTR 4b/a, nine studies with 1640 cases and 1268 controls on -786C > T, and 15 studies with 2660 cases and 2557 controls on + 894G > T polymorphism were selected. Pooled data revealed that eNOS VNTR 4b/a (dominant model: OR = 1.174, 95% CI 1.021-1.350, p = 0.025) and + 894G > T (allele model: OR = 1.278, 95% CI 1.024-1.595, p = 0.030; homozygote model: OR = 1.442, 95% CI 1.084-1.917, p = 0.012; dominant model: OR = 1.305, 95% CI 1.006-1.693, p = 0.045; and recessive model: OR = 1.378, 95% CI 1.045-1.817, p = 0.023) polymorphisms were significantly associated with an increased risk of RPL, but not - 786 T > C. Stratified analysis by ethnicity revealed that the eNOS + 894G > T was associated with RPL risk in Asians. CONCLUSIONS: To sum up, our results indicated that the eNOS VNTR 4b/a and + 894G > T polymorphisms might be contributing to RPL development, but not the - 786C > T polymorphism.

Association of MMP-2, MMP-3, and MMP-9 Polymorphisms with Susceptibility to Recurrent Pregnancy Loss.

BACKGROUND: Genetic causes that contribute to recurrent pregnancy loss (RPL) are not fully understood. The aim of this study was to evaluate the association of five polymorphisms at MMP-2, MMP-3, and MMP-9 genes with risk of RPL. Methods: The study comprised 250 women with RPL and 250 healthy controls. The MMP-2 (rs243865, rs2285053), MMP-3 (rs35068180), and MMP 9 (rs3918242, rs17576) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: A significant association was found between MMP-3 rs35068180 polymorphism and RPL risk. There was no significant association between RPL and polymorphisms at MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) genes. Conclusion: MMP-3 rs35068180 polymorphism may modulate RPL risk in Iranian women. There is no evidence to suggest that MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) polymorphisms are associated with RPL risk.

Cumulative Evidence for Association between IL-10 Polymorphisms and Kawasaki Disease Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis was carried out to evaluate the associations between IL-10 polymorphisms and Kawasaki disease (KD) risk. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, China National Knowledge Infrastructure and SciELO for all relevant studies evaluating IL-10 polymorphism and susceptibility to KD. The associations were measured by odds ratios (ORs) and its corresponding 95% confidence intervals (CIs). RESULTS: A total of 13 studies including four studies on -1082 A > G, four studies on -819 T > C and five studies on -592 A > C polymorphism were selected. Pooled data revealed that IL-10 -592 A > C polymorphism was significantly associated with an increased risk of KD (C vs. A: OR = 0.402, 95% CI 0.194-0.832, p = 0.014). However, IL-10 -1082 A > G and -819 T > C polymorphisms were not significantly associated with risk of KD under all five genetic models. CONCLUSIONS: Our results revealed that IL-10 -592 A > C polymorphism was associated with risk of KD, while IL-10 -1082 A > G and -819 T > C polymorphisms were not involved in the development of KD.

Association of Neuregulin 1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C Polymorphisms with Susceptibility to Non-Syndromic Hirschsprung's Disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a heterogeneous congenital malformation of the enteric nervous system with a complex genetic etiology. We investigated if there was an association between Neuregulin-1 (NRG1) rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms and the risk of HSCR. Methods: We determined and compared the frequency of NRG1 polymorphisms rs7835688 G > C, rs16879552 T > C and rs2439302 G > C in 70 children with HSCR and 90 controls by TaqMan SNPs genotyping assays. Results: No significant differences in allele or genotype frequencies of NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms were observed between HSCR cases and controls. Analyses showed that the NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms were not significantly associated with an increased risk of non-syndromic HSCR. Conclusions: Our findings suggested that NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms are not a risk factor in development of HSCR.

Association of Fetal MTHFR 677C > T Polymorphism with Non-Syndromic Cleft Lip with or without Palate Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: This study was conducted to estimate the precise association of fetal MTHFR 677 C > T polymorphism with risk of nonsyndromic cleft lip with or without cleft palate (NSCL ± P) using a large-scale meta-analysis. Methods: A comprehensive literature search was performed using studies published on PubMed, Science Direct, Scopus and CNKI databases up to November 1, 2019. Results: A total of 38 studies with 6,525 children with NSCL ± P and 8,606 controls were selected. Overall, there was a significant association between MTHFR 677 C > T polymorphism and NSCL ± P risk. Subgroup analysis by ethnicity revealed that MTHFR 677 C > T polymorphism contributed to development of NSCL ± P in Caucasian and Mixed populations, but not in Asians. When stratified by country of origin, we found a significant association in Brazilian, Turkish and Indian populations, but not in Chinese and US-American. Conclusions: This meta-analysis provides strong evidence that fetal MTHFR 677 C > T polymorphism is significantly associated with NSCL ± P risk.

Association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 Polymorphisms with Susceptibility to Kawasaki Disease: A Comprehensive Meta-Analysis.

BACKGROUND: Kawasaki Disease (KD) is a multifactorial condition at the junction of infectious diseases, immunology, rheumatology, and cardiology. The aim of this study is to derive a more precise estimation of the association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms with risk of KD. Methods: PubMed, EMBASE, CNKI databases were searched to identify all relevant studies. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using CMA 2.2 software. Results: A total of 25 studies including eleven studies on TNF-α rs1800629, five studies on CASP3 rs72689236 and nine studies on FCGR2A rs1801274 were selected. Overall, pooled data revealed that CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms were significantly associated with an increased risk of KD. However, there was no significant association between TNF-α rs1800629 and KD. Conclusions: This meta-analysis suggested that CASPS rs72689236 and FCGR2A rs1801274 polymorphisms may modulate individual susceptibility to KD.

Association of BMP4 rs17563 Polymorphism with Nonsyndromic Cleft Lip with or without Cleft Palate Risk: Literature Review and Comprehensive Meta-Analysis.

BACKGROUND: Although published individual studies have reported associations between BMP4 rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCLP) risk, the results are conflicting. This meta-analysis was conducted to assess the association based on multiple studies. Methods: A comprehensive literature search up to October 1st, 2019 was performed using PubMed, Science Direct, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Results: Fourteen case-control studies with 2,058 NSCLP cases and 2,557 controls were selected. There was no significant association between BMP4 rs17563 polymorphism and risk of NSCLP overall. Subgroup analysis revealed that BMP4 rs17563 polymorphism was associated with NSCLP risk in Chinese and Brazilian populations. Conclusions: This meta-analysis suggests that BMP4 rs17563 polymorphism was not associated with NSCLP risk in overall population. However, BMP4 rs17563 polymorphism may be a risk factor for development of NSCLP in Chinese and Brazilians.

Association of Endothelial Nitric Oxide Synthase 894G > T Polymorphism with Preeclampsia Risk: A Systematic Review and Meta-Analysis based on 35 Studies.

BACKGROUND: Several case-control studies have been performed to investigate the association between 894 G > T polymorphism in endothelial nitric oxide synthase (eNOS) gene and susceptibility to preeclampsia. However, the results were inconsistent and inconclusive. Therefore, we conducted this meta-analysis to investigate the association. Methods: All studies published up to September 30, 2019 were identified by searching electronic databases such as PubMed, EMBASE, CNKI, and WANFANG. Results: A total of 35 case- control studies with 4,254 cases and 5,801 controls were selected. There was a significant association between the eNOS 894 G > T and preeclampsia risk. When stratified by ethnicity, an increased risk of preeclampsia was found in Caucasian and Mixed populations, but not in Asians or Africans. Conclusion: Based on our meta-analysis, the eNOS 894 G > T polymorphism was associated with an increased risk of preeclampsia, especially among Caucasian and Mixed populations.

An Updated and Comprehensive Meta-Analysis of Association between VEGA -634G > C, -460T > C, +405G > C and +936C > T Polymorphisms and Retinopathy of Prematurity Risk.

BACKGROUND: Previous studies have suggested an association between VEGF-A polymorphisms and retinopathy of prematurity (ROP) risk. But the conclusions are still controversial. The aim of this meta-analysis was to evaluate the association between the VEGF-A polymorphisms and susceptibility of ROP. Methods: We searched PubMed, Scopus, WanFang and CNKI databases for all eligible case-control studies published before September 30, 2019. Results: A total of 27 case-control studies with 5,748 ROP cases and 6,146 controls were selected. The results suggested that there was an association between VEGF-A -460T > C polymorphism and increased risk of ROP under the allele model (C vs. T: OR= 0.879, 95% CI 0.776-0.994, p = 0.040). However, VEGF-A -634G > C, +405G > C and +936C > T polymorphisms were not significantly associated with risk of ROP. The subgroup analysis demonstrated that VEGF-A +405G > C polymorphism was associated with ROP risk in Caucasians. Conclusions: This meta-analysis indicates that VEGF-A -460T > C polymorphism may contribute to the susceptibility for ROP.

Association of MTHFR 1298A > C Polymorphism with Susceptibility to Non-Syndromic Cleft Lip with or without Palate: A Case-Control Study and Meta-Analysis.

BACKGROUND: Several studies have evaluated association of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene 1298A > C polymorphism with non-syndromic cleft lip with or without palate (NSCL ± P) susceptibility, however the results are inconsistent. MATERIALS AND METHODS: To address this issue, we performed a case-control study to evaluate the association of MTHFR 1298A > C polymorphism with NSCL ± P risk, followed by a meta-analysis. RESULTS: Including our study, a total of 22 case-control studies with 2,814 cases and 4,199 controls were selected. The results suggested that there was no significant association between MTHFR 1298A > C polymorphism and NSCL ± P risk overall. The subgroup analysis demonstrated that the polymorphism was significantly associated with NSCL ± P risk in Asians and Iranian populations, but not in Caucasians, mixed and Chinese populations. CONCLUSION: This meta-analysis indicates that MTHFR 1298A > C polymorphism may not contribute to NSCL ± P risk in overall. However, the MTHFR 1298A > C polymorphism was significantly associated with an increased risk of NSCL ± P in Asians and Iranian populations.

Association of IL-6 -174G > C and -572G > C Polymorphisms with Risk of Legg-Calve-Perthes Disease in Iranian Children.

BACKGROUND: Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head with multifactorial etiology. The aim of this study was to analyze the association of IL-6 polymorphisms with LCPD risk in Iranian children. Methods: The study comprised of 45 children diagnosed with LCPD and 60 healthy subjects. The IL-6 -174 G > C and -597 G > C polymorphisms were genotyped by PCR-RFLP assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. Results: The mutant homozygote genotype (CC) of IL-6 -174 G > C polymorphism was associated with increased risk of LCPD (OR 3.554; 95% CI: 0.1.578-8.004; p = 0.002). There was no significant association between IL-6 -597 G > C polymorphism and an increased risk of LCPD. Conclusions: Our results suggest that the IL-6 -174 G > C but not the IL-6 -597 G > C polymorphism may increase LCPD susceptibility in Iranian children.