Chinese Zhuang Population Research Articles

Genetic structure and paternal admixture of the modern Chinese Zhuang population based on 37 Y-STRs and 233 Y-SNPs

The Zhuang are the largest minority group in China and the aboriginal people of the Guangxi Zhuang Autonomous Region. Over thousands of years, the gene pool of the Zhuang has been shaped by the genetic admixture with the Han Chinese. However, little is known about the paternal genetic structure of the modern Zhuang people. Here, we used a high-resolution panel comprising 233 Y-chromosomal single-nucleotide polymorphisms (Y-SNPs) and 37 Y-chromosomal short tandem repeats (Y-STRs) to illuminate the paternal genetic structure and affinities of the Zhuang population. Their Y-SNP haplogroup diversity reached 0.9580 with 44 different subhaplogroups and their Y-STR haplotype diversity reached 1.0. Several bioinformatics analyses were conducted comparing the Zhuang to various reference populations worldwide. Mismatch analysis suggested extensive intermarriages between the Zhuang and O2-dominant groups such as the Han. Genetic clustering analysis of Y-STRs revealed broad genetic affinities between the Zhuang and several geographically, linguistically, and the ethnically related groups such as the southern Han, Bouyei, Li, Miao, and Yao from China. Principal Component Analysis of Y-SNPs demonstrated long-term close genetic relationships among the Zhuang people, Hainan Han, Guangdong Han, and Southeast Asians. Combined Y-STR/Y-SNP analysis showed the Zhuang people and the Hainan Han share common ancestry, illuminating the patrilineal descent of the Zhuang and lending genetic support to commonly accepted ideas regarding the origin of the Hainan Han. Our analysis of Y-SNPs and Y-STRs not only revealed the fine-scale genetic structure of the Zhuang population, but also illuminated their paternal derivation, which is defined by the common ancestry with the Hainan Han, the introgression of southern Chinese groups such as the Han, Bouyei, Li, Miao, and Yao, the long-term phylogenetic relationships with Southeast Asians.

Association between AKT2 gene polymorphism and polycystic ovary syndrome: a case-control study

Objective This study was conducted to understand the association between the AKT2 (AKT serine/threonine kinase 2) gene polymorphism (rs2304186) and PCOS. Methods In total, 1287 participants were included. Six genotype models (Dominant model: TT + TG vs. GG; Recessive model: TT vs. TG + GG; Over-dominant model: TT + GG vs. TG; Co-dominant model: TT vs. TG; Co-dominant TT vs. GG; Allele analysis: T vs. G) were applied in the analysis. According to the races and obesity, subgroup analyses were also performed. Results No significant association between rs2304186 and PCOS was identified in the whole sample or the Han groups, even after multi-adjustments. Only in the Zhuang groups was it suggested that rs2304186 might promote the risk of PCOS to some extent (Unadjusted: Over-dominant TT + GG vs. TG, OR = 1.522, 95%CI = 1.076–2.152, p = .018; Age-adjusted: Over-dominant TT + GG vs. TG, OR = 1.543, 95%CI = 1.069–2.228, p = .021; Multi-adjusted: OR = 1.497, 95%CI = 1.024–2.188, p = .037). The risk effect was also detected in the non-obesity group (BMI <24.0 kg/m2) for the Co-dominant model (TT vs. TG: OR = 1.355, 95%CI = 1.001–1.835, p = .050). Conclusions In summary, we first discovered that rs2304186 might significantly elevate the PCOS risk, especially in the Chinese Zhuang population and the non-obesity group. Further studies are needed to confirm these results.

The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population

Minichromosome maintenance complex component 6 (MCM6) is involved in tumorigenesis of hepatocellular carcinoma (HCC). Because its effect on different populations remains unclear, this study investigated the impact of MCM6 on HCC in Southern Chinese Zhuang population. In addition to assessing the global mRNA levels of MCM6 based on The Cancer Genome Atlas database (TCGA) and The Gene Expression Omnibus database (GEO), associations between MCM6 mRNA levels and clinicopathological features were analyzed. High MCM6 levels were associated with high alpha-fetoprotein (AFP) (>20 ng/mL in serum) (P < 0.0001) and advanced clinical stage (III + IV) (P < 0.001). Higher MCM6 was associated with poorer outcomes (P < 0.01) in these databases. Furthermore, the mRNA and protein expression of MCM6 in the Guangxi Zhuang population was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC). The results showed that MCM6 levels were up-regulated in the Zhuang population with HCC. Higher MCM6 protein levels were correlated with larger tumor size (>5 cm) (P = 0.038) and advanced clinical stage (III + IV) (p = 0.023). Bioinformatic enrichment analysis of MCM6 and its interacting proteins (CDT1,WEE1,TRIM28 and MKI67) suggested that in addition to being involved in the cell cycle process, these complexes could also be involved in protein binding, pre-replication complex assemble, and nucleus metabolism. Based on the protein-protein interaction (PPI) network with module screen, the interactions between MCM6 and its potential interacting proteins were further studied through protein docking with hot spot analysis. Additionally, the results of the algorithms combining the ROC of MCM6 and its interacting proteins showed that combination biomarker analysis has better HCC diagnosis ability than the single MCM6 test. The combination of MCM6 and TRIM28 was more suitable for the Guangxi Zhuang population. Overall, our study suggests that MCM6 plays an important role in the growth of HCC. MCM6 could be an optimal biomarker for diagnosing HCC and a potential molecular target for HCC therapy in the Zhuang population.

Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.

BackgroundAsthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome‐wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS‐supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population.MethodsA case‐control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa).ResultsThe distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048‐3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001‐4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls.Conclusionrs3117098 may be the risk factor for asthma in Chinese Zhuang population.

Association between interleukin-35 polymorphisms and coronary heart disease in the Chinese Zhuang population: a case-control study.

Inflammatory cytokines play an important role in the pathogenesis of cardiovascular disease. Few studies have investigated the association between interleukin-35 (IL-35) genetic variants and the risk of coronary heart disease (CHD). We examined the association between IL-35 polymorphisms and CHD in the Chinese Zhuang population. A total of 707 CHD patients and 707 age-matched and sex-matched controls were enrolled in this case-control study. Genotypes of the single nucleotide polymorphisms (SNPs) of IL-35, including rs428253, rs6613, rs9807813, rs2243115, rs568408, rs582054, rs583911, rs4740, and rs393581, were examined by MassArray. Plasma IL-35 level was measured using an enzyme-linked immunosorbent assay. The multivariate logistic regression model was used to evaluate the association between the SNPs and the risk of CHD. In the Chinese Zhuang population, compared with the GG genotype of EBI3 rs428253, individuals with the CC genotype had a 2.02-fold (95% confidence interval: 1.07-3.84, P=0.031) higher risk of CHD. Further adjustment for potential risk factors did not alter the positive association (CC vs. GG, odds ratio=2.30, 95% confidence interval: 1.16-4.54, P=0.042). SNPs rs4740, rs2243115, rs568408, and rs582054 were not statistically related to the risk of CHD. The plasma IL-35 levels showed a marginally significant difference between rs428253 genotypes [GG: 13.39 (7.89-19.25) vs. CC+GC: 17.53 (8.98-22.56) pg/ml, P=0.057]. The EBI3 rs428253 CC genotype was associated with an increased risk of CHD in the Chinese Zhuang population, although no significant difference in IL-35 levels was observed between genotypes in healthy controls.

Allelic and haplotype diversity of HLA-A, HLA-B and HLA-DRB1 gene at high resolution in the Nanning Han population.

The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA-A, HLA-B and HLA-DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA-A, 56 HLA-B and 31 HLA-DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence-based typing method. Of these, the three most common alleles in HLA-A, HLA-B and HLA-DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA-DRB1, the p values of the HLA-A and HLA-B loci showed that the HLA allelic distribution in this population was in accordance with Hardy-Weinberg expectation (p>0.05). A total of 173 HLA~A-B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA-A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA-A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA-A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population.

The association of RAR-related orphan receptor A (RORA) gene polymorphisms with the risk of asthma.

Asthma is a common, heterogeneous chronic respiratory disease characterized by chronic inflammation of the airway, airway hyperreactivity, and airway remodeling. The RAR-related orphan receptor A (RORA) gene has been identified for the pathogenesis of asthma. The purpose of this research was to investigate the relationship between RORA gene polymorphisms and asthma susceptibility in the Chinese Zhuang population. This was a case-control study including 231 children with asthma and 343 healthy controls. The RORA gene polymorphisms were measured by the polymerase chain reaction-ligase detection reaction genotyping assays and confirmed by sequencing. The distribution of the genotype frequencies of the RORA rs11071559 C>T was significantly different in the group of cases and the healthy children (P<0.05). By haplotype analyses, the haplotype TT (rs7164773/rs11071559) was statistically significant between asthmatics and nonasthmatics, but the association was not significant after correction for multiple comparisons. Our results provided evidence that the RORA rs11071559C>T polymorphism was associated with an elevated susceptibility to pediatric asthma in the Chinese Zhuang population.

The prevalence and molecular characterization of (δβ)0 -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population.

ObjectiveTo reveal the prevalence and molecular characterization of (δβ)0‐thalassemia [(δβ)0‐thal] and hereditary persistence of fetal hemoglobin (HPFH) in the Chinese Zhuang population.MethodsA total of 105 subjects with fetal hemoglobin (Hb F) level ≥5% from 14 204 unrelated ones were selected for the study. Multiplex ligation dependent probe amplification was firstly used to analyze dosage changes of the β‐globin gene cluster for associated with (δβ)0‐thal and HPFH mutations. The gap polymerase chain reaction was then performed to identify the deletions using the respective flanking primers. Hematologic data were recorded and correlated with the molecular findings.ResultsTwenty‐one (0.15%) subjects were diagnosed with Chinese Gγ(Aγδβ)0‐thal. Nine (0.06%) were diagnosed with Southeast Asia HPFH (SEA‐HPFH) deletion. Seventy‐five (0.53%) cases remained uncharacterized. Three genotypes for Chinese Gγ(Aγδβ)0‐thal and SEA‐HPFH deletion were identified, respectively. The genotype‐phenotype relationships were discussed.ConclusionOur study for the first time demonstrated that (δβ)0 and HPFH were not rare events, and molecular characterized Gγ(Aγδβ)0‐thal and HFPH mutations in the Chinese Zhuang population. The findings in our study will be useful in genetic counseling and prenatal diagnostic service of β‐thalassemia in this populations.

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p < 0.05), without correlation with age, gender, smoking, drinking, tumor size, serum alpha-fetoprotein level, hepatitis B virus infection, metastasis, and invasion (p > 0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

The association between four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) and fetal hemoglobin levels in Chinese Zhuang β-thalassemia intermedia patients

Four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) associated with HbF levels have been identified in different populations worldwide. To explore whether these SNPs modulate HbF expression in Chinese Zhuang population, 436 Chinese Zhuang β-thalassemia intermedia (β-TI) patients were divided into high HbF level group (mean HbF=25.5%, n=218) and low group (mean HbF=6.51%, n=218) for genotyping using PCR-HRM method. Results demonstrated that there was a significantly higher minor allele frequency (MAF=34.2%) of rs4895441 (G) in HMIP in high HbF level group than that in low group (MAF=19.8%) (P=0.001, OR=1.73, 95% CI: 1.24–2.57). The cumulative effects of risk genotypes of these loci for patients carrying any combination of 1, 2 or 3 risk genotype had a gradually increased risk of high HbF level phenotype compared to those without the risk genotypes (OR=1.50–9.06, P=0.0008); Gene-gene interaction of rs7842144 and rs4895441 showed the best model with the smallest prediction error (0.4259) and the greatest consistency of coefficient of variation (P=0.01). We concluded that rs4895441, G on HMIP might be a high-risk modifier variant for high HbF level expression, and HBG2, BCL11A and HMIP genes, as HbF quantitative trait loci (QTL) could have a synergistic effect on increasing the HbF level in Chinese Zhuang β-TI patients.

Genetic variation in the 3'-untranslated region of PAK1 influences schizophrenia susceptibility.

The present study aimed to investigate the association of two polymorphisms (rs2844337 and rs11237200) in the P21 protein (cell division control protein 42/Rac)-activated kinase 1 gene with susceptibility to schizophrenia (SCZ) in Chinese Zhuang and Chinese Han populations. A total of 700 patients with SCZ and 700 healthy controls were recruited. Rs2844337 and rs11237200 polymorphisms were genotyped using Sequenom technology. A total of 591 patients completed the Positive and Negative Syndrome Scale (PANSS) assessment. Data were statistically analyzed using PLINK version 1.07 and SPSS version 17.0. In the Chinese Han population, the genotypic (P=0.038) and allelic (P=0.033) frequencies of the 3'-untranslated region (UTR) genetic variation of rs2844337 in patients were significantly decreased compared to that in controls; these frequencies were significantly associated with SCZ susceptibility in the additive model (Padj=0.032) and in the recessive model (Padj=0.031). Moreover, the TG haplotype constructed by rs2844337 and rs11237200 polymorphisms remained significantly associated with SCZ risk following adjustment for gender and age and applying a Bonferroni correction in the Chinese Han population (Padj=0.003, PBC=0.009). The adjacent 5'-UTR genetic variation of rs11237200 was significantly associated with the total score (Padj=0.006), positive scale score (Padj=0.014) and general psychopathology scale scores (Padj=0.009) in the recessive model of the Chinese Han population. However, these polymorphisms were not significantly associated with SCZ susceptibility or the PANSS scores in the Chinese Zhuang population. In conclusion, variations in the PAK1 gene influenced the susceptibility and severity of the clinical symptoms of SCZ in the Chinese Han population investigated in the present study.

The dopamine beta-hydroxylase gene polymorphism rs1611114 is associated with schizophrenia in the Chinese Zhuang but not Chinese Han population.

Schizophrenia (SCZ) is a devastating neurodevelopmental disorder. However, the mechanism underlying this highly heritable disorder remains unclear. The dopamine beta-hydroxylase (DBH) gene encodes a key metabolic enzyme of dopamine. Consequently, DBH is considered a candidate gene for SCZ. However, previous studies on its association with SCZ susceptibility have shown conflicting results. Here, we examined association between the rs1611114 polymorphism of DBH and SCZ susceptibility and related clinical symptoms. A total of 691 SCZ patients and 698 age- and gender-matched healthy controls were examined. mRNA expression levels of DBH were measured by quantitative real-time polymerase chain reaction, and the rs1611114 polymorphism was genotyped using the Sequenom MassARRAY platform. Also, the Positive and Negative Syndrome Scale (PANSS) was used to assess SCZ clinical symptoms. Our results show lower DBH mRNA expression levels in SCZ patients than healthy controls (Zhuang: p=0.000; Han: p=0.037). Interestingly, the rs1611114 polymorphism was significantly associated with SCZ susceptibility (overdominant model: p=0.010) in only the Chinese Zhuang population. Furthermore, the rs1611114 polymorphism was associated with PANSS total score (allele T/C: p=0.015) and general psychopathology score (allele T/C: p=0.027) in Chinese Zhuang SCZ patients. These results suggest that the DBH gene may play an important role in the occurrence of SCZ. Also, rs1611114 may be associated with SCZ susceptibility and related clinical symptoms in the Chinese Zhuang but not Han Chinese population. Further studies with larger samples of different ethnicities are needed to confirm the role of DBH in SCZ.

Association between ABO blood groups and coronary heart disease in Chinese Guangxi Zhuang population

To investigate this association between ABO blood groups and coronary heart disease (CHD) in the Chinese Guangxi Zhuang population. From August 2010 to April 2013, we performed a case-control study in a Chinese Zhuang population, which included 1 024 CHD cases and 1 024 age and gender-matched non-CHD controls. The ABO blood groups and biological variables were measured by standard laboratory procedures. The Gensini score was used to evaluate the severity of coronary artery stenosis. Compared to non-CHD control group, CHD group had higher levels of fasting blood glucose ((6.71 ± 6.72) mmol/L vs. (4.98 ± 1.55) mmol/L, P < 0.001), LDL-C ((2.89 ± 1.18) mmol/L vs. (2.60 ± 1.05) mmol/L, P = 0.002) and CRP ((7.74 ± 7.32) mg/L vs. (2.93 ± 2.19)mg/L, P < 0.001) as well as higher proportion of history of hypertension (57.0% vs. 27.5%, P < 0.001), history of diabetes (29.6% vs. 9.6%, P < 0.001), family history of CHD (35.3% vs. 10.6%, P < 0.001) and smoking (51.0% vs. 38.2%, P < 0.001). Logistic analysis indicated that ABO blood groups were associated with CHD risk in the Chinese Zhuang population. Compared with group O, the group B individuals had a higher risk of CHD (OR = 2.33, 95% CI 1.88-2.90, P < 0.001), this result remained after adjustment for the conventional CHD risk factors (OR = 1.55, 95% CI 1.05-2.52, P = 0.047). In addition, there were significant differences of Gensini score between non-O subjects and group O subjects in the CHD group, and MACE at 1-year follow-up was similar between ABO blood groups of CHD individuals. ABO blood groups are associated with CHD risk in the Chinese Zhuang population.

Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population

Background and objectiveInterleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual’s susceptibility to hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with HBV-related HCC in a Chinese population. MethodsThe +114T/G and −384T/G polymorphisms in the IL-2 gene were examined in 115 cases of chronic hepatitis B (CHB), 67 cases of HBV-related liver cirrhosis (LC), 107 cases of HBV-related HCC, and 105 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). ResultsWe found that there were significant differences in the genotype and allele frequencies of the IL-2 gene +114T/G polymorphism between the HBV-related HCC patients and the healthy controls. The +114 TG and GG genotypes were associated with a significant increased HCC risk as compared with the TT genotype (OR=1.988, 95% CI, 1.034–3.480, P=0.009 for TG genotype, and OR=1.975, 95% CI, 1.012–3.341, P=0.013 for GG genotype, respectively). The +114 G allele was correlated with a significant increased HCC risk as compared with the T allele (OR=1.423, 95% CI, 1.023–1.975, P=0.031). In addition, we found significant decreased serum IL-2 in HBV-related HCC patients (288.6±177.1ng/L) compared with healthy controls (238.2±136.7ng/L) (t=2.32, P=0.021). Genotypes carrying the +114 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in HBV-related HCC patients. ConclusionThe results suggested that the IL-2 +114T/G polymorphism may contribute to increased HBV-related HCC risk through regulating the serum IL-2 levels. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

Association between the NOTCH4 gene rs3131296 polymorphism with schizophrenia risk in the Chinese Zhuang population and Chinese Han population.

Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations. To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case-control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations. The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples. Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ.

Study about the Relationship between TNF-Α-308G/A and Essential Hypertension in Specific Population-Taking Chinese Minority Zhuang in Guangxi as an Example

objective: study the association between TNF gene and essential hypertension (EH) in Chinese minority Zhuang population. Method: select 170 normal as control group and 246 patients with EH as an object of study, use polymerase chain reaction - restriction fragment length polymorphism method to analyze polymorphic loci in the promoter region of TNF-α gene-308G / A allele, and genotype frequency distribution characteristics were analyzed, and the relationship between genetic susceptibility polymorphisms and EH was given.

Association of transcription factor FOXP3 gene polymorphism with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population

To investigate the association of single nucleotide polymorphisms(SNP) of FOXP3 gene with susceptibility to systematic lupus erythematosus (SLE) in Chinese Zhuang population. Author analyzed the -2383 C/T and -3281 C/A two SNPs of the FOXP3 gene promoter in 120 patients with SLE and 160 age and sex matched controls in a Chinese Zhuang population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing. The distribution of the FOXP3 gene -3281 C/A polymorphism was not different between the two groups. However, the FOXP3 gene -2383 C/T polymorphism was significantly different (P<0.05) between the two groups. The relative risk of suffering from SLE of -2383T allele carriers was 1.715 times of the -2383C allele carriers (OR=1.715, 95%CI: 1.165-2.525). Consistent with the results of the genotyping analyses, the FOXP3 -2383T/-3281A haplotype frequency in patients with SLE was significantly higher than that in controls (P<0.05). The -2383T/-3281A allele was associated with a significantly increased risk of SLE (OR=2.196, 95%CI: 1.165-4.142). The FOXP3 gene -2383C/T polymorphism is associated with SLE, and the -2383T allele is risk factor for SLE in the population studied.

12 - Investigation and Management of Megaloblastic Anaemia

Four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) associated with HbF levels have been identified in different populations worldwide. To explore whether these SNPs modulate HbF expression in Chinese Zhuang population, 436 Chinese Zhuang β-thalassemia intermedia (β-TI) patients were divided into high HbF level group (mean HbF = 25.5%, n = 218) and low group (mean HbF = 6.51%, n = 218) for genotyping using PCR-HRM method. Results demonstrated that there was a significantly higher minor allele frequency (MAF = 34.2%) of rs4895441 (G) in HMIP in high HbF level group than that in low group (MAF = 19.8%) (P = 0.001, OR = 1.73, 95% CI: 1.24–2.57). The cumulative effects of risk genotypes of these loci for patients carrying any combination of 1, 2 or 3 risk genotype had a gradually increased risk of high HbF level phenotype compared to those without the risk genotypes (OR = 1.50–9.06, P = 0.0008); Gene-gene interaction of rs7842144 and rs4895441 showed the best model with the smallest prediction error (0.4259) and the greatest consistency of coefficient of variation (P = 0.01). We concluded that rs4895441, G on HMIP might be a high-risk modifier variant for high HbF level expression, and HBG2, BCL11A and HMIP genes, as HbF quantitative trait loci (QTL) could have a synergistic effect on increasing the HbF level in Chinese Zhuang β-TI patients.