Polymorphisms of the DNA repair gene xeroderma pigmentosum groups A and C and risk of esophageal squamous cell carcinoma in a population of high incidence region of North China

Aim Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity (DRC) and genetic susceptibility to different cancers. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum group A (XPA) and XPC can influence the risk of esophageal squamous cell carcinoma (ESCC). Methods In this report, one SNP of XPA and three SNPs of XPC were genotyped by polymerase-chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) assay in 327 ESCC patients and 612 healthy controls in a high incidence region of North China. Results Family history of upper gastrointestinal cancers (UGIC) may increase the risk of developing ESCC. The overall genotype and allelotype distributions of XPA A23G in ESCC patients were significantly different from that in healthy controls (P < 0.05). The A/G + G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype. When stratified for family history of UGIC, compared with A/A genotype, A/G + G/G genotype significantly decreased the risk of ESCC in groups with negative history of UGIC. The overall genotype and allelotype distributions of XPC intron 9 PAT^+/- and exon 15 Lys939Gln and exon 8 Val499Ala in ESCC patients were not significantly different from that in healthy controls (P > 0.05). When stratified for smoking status and UGIC family history, compared with A/A genotype, C/C genotype of exon 15 Lys939Gln significantly increased the risk of developing ESCC in non-smoker group. Conclusions We concluded that XPA23 polymorphism may be useful markers for identifying individuals at risk of developing ESCC. C/C genotype of XPC exon 15 may be one of the factors that affect the risk of developing ESCC in nonsmoking population in the high incidence region of China.     

NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China

AIM: To investigate the association of the NQO1 (C609T)polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China.METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls.RESULTS: The NQO1 C609T C/C, c/r and T/T genotype frequency among healthy controls was 31.5 %, 52.1% and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (X2=4.79, P=0.028). The NQO1T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes,with an age, sex and smoking status adjusted odds ratio (OR)of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 %CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC.CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.     

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome‐wide association studies have identified that the rs2274223 single‐nucleotide polymorphism inphospholipase C epsilon 1 and the single‐nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high‐resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.08–3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR = 0.71, 95% CI = 0.52–0.97) and no significant association in the older group (OR = 1.19, 95% CI = 0.87–1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case–control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.     

核黄素转运蛋白C20orf54基因rs3746804位点单核苷酸多态性与食管鳞癌遗传易感性的关系

  目的 探讨核黄素转运蛋白C20orf54基因外显子3中rs3746804位点单核苷酸多态性（SNP）与食管鳞癌（ESCC）遗传易感性的关系。方法 磁珠法提取全血基因组DNA,以直接测序方法对434例包括长治、林州两地ESCC患者与554例包括长治、林州健康人群及由林州移居长治的健康移民5组人群的C20orf54基因外显子3的SNP1139C>T进行基因分型。结果 长治ESCC组与长治健康组、健康移民组在基因型CT(37.5%比51.0%、37.5%比52.0%)、CC(44.2%比34.8%、44.2%比33.0%)的分布频率上差异明显（P值均<0.05）,与林州ESCC组在基因型TT(18.3%比4.1%)、CC(44.2%比54.6%)的分布频率上有明显差异（P值均<0.05）;林州ESCC组与健康移民组在基因型TT(4.1%比15.0%)、CT(41.2%比52.0%)、CC (54.6%比33.0%)的分布频率上差异明显（P值均<0.05）,与长治健康组在基因型TT(4.1%比14.1%)、CC(54.6%比34.8%)的分布频率上差异明显（P值均<0.01）。肿瘤组（长治ESCC组+林州ESCC组）与健康组（长治健康组+林州健康组+健康移民组）在基因型CT(39.2%比48.7%)和CC (48.8%比38.2%)的分布频率上差异明显（P值均<0.01）。相对于CC基因型,CT和CT+TT基因型可以降低食管癌发生的危险性（OR=0.630,95%CI 0.481~0.826;OR=0.654,95%CI 0.507~0.844）。结论 C20orf54基因外显子3中rs3746804 位点的SNP与食管鳞癌的遗传易感性明显相关。     

NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China

AIM: To investigate the association of the NQO1 (C609T) polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China. METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls. RESULTS: The NQO1 C609T C/C, C/T and T/T genotype frequency among healthy controls was 31.5 %, 52.1 % and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (chi(2)=4.79, P=0.028). The NQO1 T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes, with an age, sex and smoking status adjusted odds ratio (OR) of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 % CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC. CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.     

Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China

AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China. METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203 ESCC and 152 GCA) and 443 healthy controls. RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42 and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively). Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10, 95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%, 39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6% and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P>0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95% CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46) in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes. CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.     

PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China

SUMMARY. PTEN, as a tumor suppressor gene, plays an important role in regulating cell growth, proliferation, and apoptosis. Two common polymorphisms, –9C/G and IVS4 (?/+), may alter susceptibility to the disease. To test the hypothesis that the genetic variations of PTEN play a role in the etiology of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), a population‐based case‐control study was conducted in 350 ESCC patients, 257 GCA patients, and 634 healthy controls from a high‐incidence region of Hebei province, China. The PTEN polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism analysis (PCR‐RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age, gender and smoking status adjusted OR = 1.73 and 1.67; 95% CI = 1.29–2.32 and 1.28–2.19, respectively). The overall distribution of the PTEN –9C/G genotype was not significantly different between cancer patients and controls. Compared with the PTEN IVS4‐/? genotype, the IVS4+/+ genotype significantly decreased the risk of ESCC and GCA development, the adjusted OR was 0.64 (95% CI = 0.44–0.94) and 0.63 (95% CI = 0.41–0.98), respectively. Stratification analysis by gender, age, smoking status and family history of UGIC showed that the PTEN IVS4?/+ genotype only reduced the risk of ESCC (adjusted OR = 0.55, 95%CI = 0.34–0.90) among subjects with family history of UGIC. While the IVS4+/+ genotype decreased the susceptibility to both ESCC and GCA (adjusted OR = 0.61 and 0.57, 95% CI = 0.37–0.98 and 0.34–0.98, respectively) among male subjects, the IVS4+/+ genotype only decreased the risk of ESCC development among subjects younger than 55 years (adjusted OR = 0.43, 95% CI = 0.21–0.85). In addition, the haplotype analysis found that the –9C/IVS4– haplotype increased the risk of developing ESCC and GCA (OR = 1.31 and 1.24, 95% CI = 1.08–1.58 and 1.001–1.53). Our results suggested that the PTEN IVS4+/+ homozygote may play a protective role in the development of ESCC and GCA, while the haplotype –9C/IVS4– might be the risk factor of the development of ESCC and GCA in the high incidence region population of Hebei province, China.     

No association of the matrix metalloproteinase 1 promoter polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in northern China

AIM: To investigate association of the 2Gor1Gsingle nudeotide polymorphism (SNP) in matrix metalloproteinase 1 (MMP1) promoter with susceptibility to esophageal squam-ous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of North China. METHODS: MMP1 promoter SNP was genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 healthy controls. RESULTS: The genotype frequencies of the MMP1 promoter SNP in healthy controls were 55.4% (2G/2G), 30% (1G/2G) and 14.6% (1G/1G), respectively. The genotype and allelotype distribution in ESCC and GCA patients was not significantly different from that in healthy controls (all lvalues were above 0.05). Compared with the 1G/1Ggenotype, neither the 2G/2Gnor in combination with the 1G/2G genotype significantly modified the risk of developing ESCC and GCA, the adjusted odds ratio was 1.28 (95%CI = 0.78-2.09), 1.23 (95%CI = 0.38-2.05) in ESCC and 1.39 (95%CI = 0.80-2.41), 1.34 (95%CI = 0.74-2.40) in GCA, respectively. When stratified by smoking status and family history of upper gastrointestinal cancer, the 2G/2Ggenotype alone or in combination with the 1G/2G genotype also did not show any significant influence on the risk of ESCC and GCA development. In addition, influence of the MMP1 SNP on lymphatic metastasis in ESCC and GCA was also not obs-erved. CONCLUSION: The 2Gor 1GSNP in the MMP1 promoter might not modify the risk of ESCC and GCA development and might not be used as a stratification marker to predict the potential of lymphatic metastasis in these two tumor types.     

Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population

Purpose Folate deficiency is considered to increase the risk of developing esophageal cancer. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. A single C T substitution at nucleotide 677 of the MTHFR cDNA influences enzyme activity. The purpose of this study is to compare the association of the MTHFR C677T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC).Methods Using real-time PCR and melting curve analysis, the MTHFR C677T genotypes were determined in 430 patients with ESCC (241 German Caucasians and 189 northern Chinese) and 397 unrelated healthy controls (256 German Caucasians and 141 northern Chinese).Results A significant difference in MTHFR C677T genotype distribution was observed between German Caucasian controls (C/C, 41.8%, C/T, 44.9%, T/T, 13.3%) and northern Chinese controls (C/C, 17.7%, C/T, 38.3%, T/T, 44.0%) (²=52.19, P<0.001). The distribution of the MTHFR C677T genotypes among German ESCC patients (C/C, 39.0%, C/T, 48.1%, T/T, 12.9%) was not significantly different from that among healthy controls (²=0.531, P=0.767). In contrast, the frequency of the C/C genotype among Chinese ESCC patients (8.5%) was significantly lower than among Chinese healthy controls (17.7%) (²=6.37, P=0.012). The C/C genotype was correlated with a significantly reduced risk for the development of ESCC as compared to the combination of C/T and T/T genotypes (adjusted OR=0.38, 95% CI=0.16–0.88).Conclusions Our results suggest that, in contrast to German Caucasians, the MTHFR 677CC homozygous wild-type plays a protective role in the development of ESCC in the northern Chinese population.Abbreviations CI Confidence interval - ESCC Esophageal squamous cell carcinoma - MTHFR Methylenetetrahydrofolate reductase - OR Odds ratio - PCR Polymerase chain reaction     

Polymorphisms in promoter region of FAS and FASL gene and risk of gastric cardiac adenocarcinoma

Background and Aim: The FAS and FASL system play an important role in regulating apoptotic cell death. This study was designed to investigate the correlation of FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms with susceptibility to gastric cardiac adenocarcinoma in a population of a high‐incidence region of Hebei Province. Methods: FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 262 gastric cardiac carcinoma (GCA) patients and 524 healthy controls. Results: Family history of upper gastrointestinal cancer (UGIC) might increase the risk of developing GCA (age‐ and sex‐adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.02–1.86). The overall allelotype and genotype distributions of FAS‐1377 G/A, and FASL‐844 T/C polymorphisms in GCA patients did not significantly differ from that in healthy controls (P > 0.05). Compared with individuals with a FAS‐670 A/A genotype, individuals with an A/G genotype in a smoker group had a lower risk of developing GCA (age, sex, and family history of UGIC adjusted OR = 0.55, 95% CI = 0.34–0.88). When the genotypes of FAS and FASL single nucleotide polymorphisms (SNP) were combined to analyze, no significant correlation was found between these SNP and the risk for GCA development. Conclusion: In the high‐incidence region of Hebei Province, FAS‐1377 G/A and FASL‐844 T/C polymorphisms were not associated with the risk of GCA. However, the FAS‐670 A/G genotype might decrease the risk of GCA for smoker individuals.     

Epoxide hydrolase Tyr113His polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma in population of North China

AIM: To investigate the possible association of microsomal epoxide hydrolase (mEH) Tyr113His polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a population of North China. METHODS: The mEH Tyr113His genotypes were determined by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 257 patients with esophageal squamous cell carcinoma (ESCC) and 252 healthy subjects as a control group. RESULTS: The frequencies for Tyr and His alleles were 44.2%, 55.8% in ESCC patients, and 44.0% and 56.0% in healthy subjects, respectively. No statistic difference in allele distribution was observed between ESCC patients and controls (chi2=0.008, P=0.929). The overall genotype distribution difference was not observed between cancer cases and controls (chi2=2.116, P=0.347). Compared with Tyr/Tyr genotype, neither His/His genotype nor in combination with Tyr/His genotype significantly modified the risk of the development of ESCC, the adjusted odds ratio was 1.076 (95% CI=0.850-1.361) and 0.756 (95% CI=0.493-1.157), respectively. When stratified for sex, age, smoking status and family history of upper gastrointestinal cancer, His/His genotype alone or in combination with Tyr/His genotype also did not show any significant influence on the risk of developing ESCC. CONCLUSION: MEH Tyr113His polymorphism may not be used as a stratification marker in screening individuals at a high risk of ESCC.     

Genetic variants of the C11orf30-LRRC32 region are associated with childhood asthma in the Chinese population

Introduction and objectivesTo investigate whether genetic polymorphisms of C11orf30-LRRC32 region are associated with the development of childhood asthma in the Chinese population.MethodsA total of 732 asthma children and 824 age-matched healthy controls were included in the study. Blood samples were collected from the subjects for total IgE analysis, DNA extraction and RNA extraction. Three previously reported asthma-related SNPs were genotyped, including rs7936070 (G/T), rs7927894 (A/G), and rs6592657 (A/G). Blood samples from 50 patients and 50 controls were randomly selected to detect the mRNA expression levels of C11orf30 and LRRC32 in serum.ResultsThere were significantly different genotype frequencies between the two groups in terms of rs7936070 and rs7927894. Compared with controls, patients were found to have remarkably higher risk allele frequencies of rs7936070 and rs7927894. Genotype GG of rs7936070 was indicative of remarkably elevated total IgE level as compared with genotype TT and genotype GT. Similarly, genotype AA of rs7927894 was also associated with significantly elevated total IgE level. The serum expression of C11orf30 was significantly lower in the patients than in the controls. The C11orf30 expression was significantly correlated with the total IgE level (r = −0.463, p = 0.01).ConclusionsVariants of C11orf30 were associated with the risk of childhood asthma in the Chinese population. Besides, abnormally decreased expression of C11orf30 was detected in the serum of patients, which was correlated with the total IgE level. The C11orf30 might play a role in asthma via biological pathways involving the regulation of total serum IgE level.     

Single nucleotide polymorphism in DNA methyltransferase 3B promoter and its association with gastric cardiac adenocarcinoma in North China

AIM: To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltrans-ferase 3B(DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA). METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P=0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3B genotypes in GCA patents with or without lymphatic metastasis did not show significant difference (P= 0.42). CONCLUSION: The distribution of DNMT3B SNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.     

Contribution of germ line BRCA2 sequence alterations to risk of familial esophageal cancer in a high-risk area of India

The incidence of esophageal squamous cell carcinoma (ESCC) is very high in the northeast region of India. An earlier study from China and Iran suggested that mutations in BRCA2 gene may play a role in the etiology of familial ESCC. However, the frequency of BRCA2 gene germ line mutations and its contribution to risk of familial aggregation of ESCC in high-risk region of India are not known. In the current study of 317 cases of esophageal cancer, 92 (29%) cases had a family history of esophageal and/or other cancers. Of these 92 patients, 45 (49%) patients had a family history of esophageal cancer. The risk of developing esophageal cancer was higher in cases where family history showed occurrence of cancers in first-degree relatives (odds ratio [OR]: 3.1; confidence interval [CI]: 1.9–5.3) than in second-degree relatives (OR: 1.3; CI: 0.25–3.2). Moreover, the risk of developing esophageal cancer was higher in subjects whose predegree suffered from esophageal cancer (OR: 2.4; CI: 1.1–4.1) than from any other cancers (OR: 1.1; CI: 0.32–3.3). The subjects with family history of cancer were more likely to develop ESCC if they were tobacco chewers (OR: 4.2; CI: 2.1–5.8) and betel quid users (OR: 3.6; CI: 1.8–4.6). Screening for mutations of the BRCA2 gene in the germ line DNA was carried out for 20 familial and 80 nonfamilial ESCC patients. One hundred unrelated healthy controls from the same population were included in this study. Nonsynonymous variants in exon 18 (K2729N) and exon 27 (I3412V) of BRCA2 gene were found in 3 of 20 patients with familial ESCC. No sequence alterations were found in 80 nonfamilial ESCC cases ( P = 0.01) and 100 healthy controls ( P = 0.0037), suggesting that germ line BRCA2 gene mutation may play a role in familial aggregation of ESCC in high-risk region of India.     

A study on the association between C1GALT1 polymorphisms and the risk of Henoch–Schönlein purpura in a Chinese population

Henoch–Schönlein purpura (HSP) is the most common systemic vasculitis of childhood. The molecular etiology of HSP is not well understood. The purpose of this study is to investigate the association between polymorphisms in C1GALT1 gene and the risk of HSP in a Chinese population. A total of unrelated 542 northern Chinese were enrolled in this study. PCR-RFLP method was used to genotype the five tagging SNPs in the C1GALT1 gene. Chi-squared test and logistic regression analysis were used for the comparison of genotype distribution between cases and controls. The five tagging SNPs were all in Hardy–Weinberg equilibrium in controls. SNP7 was significantly associated with HSP risk, P = 0.005. The DI genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 1.72; 95 % CI 1.11–2.67). The II genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 3.39; 95 % CI 1.16–9.30). Other SNPs were not associated with HSP risk. Variations in the C1GALT1 gene were found to be associated with HSP risk. Further studies are warranted to validate our findings and to investigate into its underlining mechanism.     

FOXP2基因多态性与功能性构音障碍的关系

目的 探讨FOXP2基因多态性与功能性构音障碍(FAD)的关系.方法 选择轻度FAD患儿42例(轻度FAD组)、中重度FAD患儿108例(中重度FAD组),同期选择140例正常健康体检者作为对照组.采用PCR-RFLP结合直接测序法测定各组FOXP2基因5′调控区3个单核苷酸多态位点(SNPs) rs923875、rs1852469和rs2396722的等位基因和基因型频率,同时构建单倍型.结果 轻度FAD组rs1852469位点4例,对照组rs2396722位点2例、rs1852469位点3例样本未能成功分型.其余FOXP2基因3个SNPs的等位基因和基因型频率均符合Hardy-Weinberg平衡定律.中重度FAD组rs1852469位点的等位基因及基因型频率与正常对照组比较有明显统计学意义(P＜0.05).单倍型rs923875A/+rs2396722T/+rs1852469T在中重度FAD组的频率显著高于正常对照组(P＜0.05).单倍型rs923875C/+ rs2396722C/+ rs1852469A在正常对照组的频率显著高于中重度FAD组,为保护性单倍型(P＜0.05).结论 FOXP2基因可能与中重度FAD有关;含有rs923875A/+ rs2396722T/+ rs1852469T单倍型的个体发生FAD的相对风险较高.     

Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G are associated with a reduced risk of preeclampsia in Maya-Mestizo women

Preeclampsia, a common complication of pregnancy, is characterized by elevated blood pressure and proteinuria developing after 20 weeks' gestational age. Susceptibility to this syndrome is believed to have a genetic component. The aim of this study was to investigate whether or not the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and glutathione S-transferase P1 (GSTP1) A313G polymorphisms are associated with preeclampsia in Maya-Mestizo women. A case-control study was performed, in which 125 preeclamptic patients and 274 healthy controls were genotyped for the MTHFR C677T and GSTP1 A313G polymorphisms by real-time PCR allelic discrimination. Allele and genotype frequencies were compared using the chi2 tests. The MTHFR 677T allele and the 677TT genotype were significantly more frequent in the controls, suggesting an association with a decreased risk of preeclampsia (p = 0.017 and p = 0.007, respectively). Similarly, GSTP1 313GG/GC genotypes and the G allele were more frequent in controls, showing a significant association with reduced risk of preeclampsia (p = 0.008 and p = 0.013, respectively). Our results suggest, for the first time, that the MTHFR 677T and GSTP1 313G polymorphisms confer a significantly decreased risk of developing preeclampsia in the Mexican Maya-Mestizo population.