Genetic polymorphisms of C3 and Bf in the Chinese population

The distribution of C3 and Bf in a Chinese population sample has been investigated. In a total of 388 individuals, 385 SS and 3 FS C3 phenotypes were observed and the following gene frequencies calculated: C3F = 0.0039, C3S = 0.9961. In 200 unrelated individuals, 155 S, 38 FS, 6 F and 1 FS 0.7 Bf phenotypes were found. The gene frequencies calculated from these were BfS = 0.8700, BfF = 0.1275, BfS0.7 = 0.0025.     

Genetic polymorphisms of 12 X-STR for forensic purposes in Shanghai Han population from China

X-chromosomal short tandem repeats (X-STR) loci are used for forensic practice in recent years in some complex kinship cases. The commercially available kit of Investigator Argus X-12 (Qiagen, Hilden, Germany) makes it possible to examine the markers of DXS10148–DXS10135–DXS8378, DXS7132–DXS10079–DXS10074, DXS10103–HPRTB–DXS10101 and DXS10146–DXS10134–DXS7423, which belong to four linkage groups of X-chromosome. In this study, a total of 309 unrelated individuals (200 males and 109 females) from Shanghai Han population were successfully analyzed with this kit. Hardy–Weinberg equilibrium tests demonstrated no significant deviation from expected values (P > 0.05) for all of the 12 X-STR loci in the Shanghai Han population. Linkage disequilibrium tests were performed for all pairs of loci by the Arlequin v3.1 software and only DXS10103–DXS10101 remained significant after adjustment for multiple testing (P < 0.05/66). The combined power of discrimination in males (CDP_M) was 0.999999996 while in females (CDP_F) was 0.999999999999995, and the combined mean exclusion chance in duo cases (CMEC_D) was 0.999998 while in trio cases (CMEC_T) was 0.999999986. The results suggest that the twelve X-STR loci may provide high polymorphic information for paternity testing and forensic identification in Chinese Han population from Shanghai.     

The genetic association between osteoprotegerin gene polymorphisms and fracture risk in Chinese Han population

This article put the genetic association exploration of osteoprotegerin (OPG) gene polymorphisms in promoter region (A-163G, T-245G) and fracture risk first and hoped to explain the ethology of fracture. The genotyping of OPG gene polymorphisms was conducted with the method of polymerase chain reaction-restriction fragment length polymorphism in 125 fracture patients and 138 relative controls. The genotype frequencies of selected controls based on OPG gene polymorphisms were checked by the χ² test whether conformed to Hardy–Weinberg equilibrium (HWE). The relative risk was represented with odds ratio (OR) and 95% confidence interval (95% CI) between gene polymorphism and disease. The linkage disequilibrium (LD) and haplotype were also analyzed. The genotypes distributions of selected controls in OPG polymorphisms conformed to HWE. The G allele of A-163G polymorphism carriers had the tendency to suffer from fracture in the same condition, compared with A allele carriers (OR = 1.63, 95% CI = 1.04–2.55). TG and TG/GG genotypes of OPG T-245G polymorphism also showed the increased risk of fracture development, but not TT genotype (OR = 2.22, 95% CI = 1.15–4.28; OR = 2.45, 95% CI = 1.28–4.68). Likely, the mutant allele G had an abnormally higher frequency in cases than controls (14.00% and 6.16%). These two polymorphisms existed the LD and the haplotype G _-163–G _-245 obviously increased the risk of fracture. OPG A-163G, T-245G polymorphisms were associated with the onset of fracture and both the independent risk factors.     

汉族人群中22个HLA-Cw等位基因全长序列单核苷酸多态性分析

为探讨HLA-Cw (Human leukocyte antigen-Cw)基因全长序列分子遗传多态性, 文章对28个HLA-Cw基因型已知的汉族个体样本, 采用长距离PCR技术和高保真性的Pfu酶, 扩增HLA-Cw基因全长序列4.5 kb, 进行分子克隆和单倍体测序。采用群体遗传学研究方法分析了HLA-Cw等位基因全长序列中各亚区的单核苷酸多态性。结果表明: 在28个样本中共检测出22种等位基因, 序列均已提交GenBank和国际IMGT/HLA数据库并获得了认可; 其中Cw*0706、Cw*030301、Cw*140201的全长序列为首次报道, 尤其是Cw*0706内含子序列的获得, 能够重新设计对该等位基因测序分型的引物, 避免测序分型中可能对这一等位基因的漏检。将28个样本的56条单倍体序列用Clustal软件进行序列排比, 输入到DnaSP4.0进行多态性分析, 共发现244个SNPs, 10处插入/缺失多态性。对HLA-Cw等位基因各亚区多态性的分析, 发现第4内含子及以前并没有受到关注的第5外显子受到平衡选择的作用, 在进化中受到了选择压力, 预示着它们在免疫系统的进化过程中可能扮演着重要的角色。     

CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population

Background

CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whether CDKN2BAS gene polymorphisms associated with Chinese patients with IA.

Methods

We selected 200 patients(52.69?±?11.50) with sporadic IA as experimental group, 200 participants(49.99?±?13.00) over the same period to the hospital without cerebrovascular diseases as control group. Extraction of peripheral blood DNA, applying polymerase chain reaction(PCR)-ligase detection reaction (LDR) identified CDKN2BAS Single nucleotide polymorphism(SNP) locus genotype: rs6475606, rs1333040, rs10757272, rs3217992, rs974336, rs3217986, rs1063192. The differences in allelic and genotype frequencies between the patient and control groups were evaluated by the chi-square test or Fisher’s exact tests.

Results

The genotype of rs1333040 and rs6475606 shown association with sporadic IA(X²?=?8.545, P?=?0.014; X²?=?10.961, P?=?0.004; respectively);the C allele of rs6475606 showed reduction the occurrence of IA; the rs1333040 and rs6475606 associated with hemorrhage, the C allele of rs1333040 could lower the risk of hemorrhage, and rs6475606 will not, rs1333040 also associated with aneurysm size.

Conclusion

Our research shows that variant rs1333040 and rs6475606 of CDKN2BAS related to the Chinese han population of sporadic IAs occurs. This study confirms the association between CDKN2BAS and IAs.

     

The genetic polymorphisms of cathepsin S were associated with metabolic disorders in a Chinese Han population

Cathepsin S (CTSS) played an important role in the etiology of cardiovascular disease and metabolic syndrome. Few studies had been reported on the association between the polymorphisms of CTSS and metabolic disorders in Asian population. Therefore we explored the association between the polymorphisms of CTSS and metabolic disorders in a Chinese Han population. The subjects were a Chinese Han cohort with 1160 participants, and the genotyping was performed with PCR-RFLP. Polymorphism rs16827671 was associated with BMI and serum total cholesterol (P = 0.001; P = 0.02, respectively). Subjects with CT genotype of rs16827671 had a higher risk of hypercholesterolemia (OR = 1.64, 95% CI: 1.15–2.33, P = 0.006) compared with TT genotype. Subjects with AG genotype of rs11576175 had lower risks of hypertriglyceridemia and borderline hypercholesterolemia (OR = 0.52, 95% CI: 0.36–0.73, P = 0.0001; OR = 0.52, 95% CI: 0.35–0.77, P = 0.001, respectively) compared with GG genotype. Compared with the haplotype TG, haplotype TA had a lower risk of hypertriglyceridemia and a higher risk of borderline hypercholesterolemia (OR = 0.62, 95% CI: 0.44–0.88, P = 0.002; OR = 1.59, 95% CI: 1.10–2.31, P = 0.008, respectively), and haplotype CA had a lower risk of hypercholesterolemia (OR = 0.35, 95% CI: 0.18–0.68, P = 0.002). In conclusion, we found that the genetic polymorphisms of CTSS were associated with metabolic disorders in a Chinese Han population, which would enrich the knowledge on genetic mechanisms of the pathogenesis of metabolic disorders.     

Association of polymorphisms in the Chr18q11.2 locus with tuberculosis in Chinese population

A GWAS study has reported that two single nucleotide polymorphisms (SNPs) were associated with predisposition to tuberculosis (TB) in African populations. These two loci represented the long-waited GWAS hits for TB susceptibility. To determine whether these two SNPs are associated with TB in Chinese population, we attempted an replication in a cohort of over one thousand Chinese TB patients and 1,280 healthy controls using melting temperature shift allele-specific genotyping analysis. We found that only SNP rs4331426 was significantly associated with TB in Chinese population (p = 0.011). However, the effect was opposite. The G allele of the SNP in Chinese population is a protective allele (OR = 0.62, 95 % CI 0.44–0.87), while it was the risk allele for African population (OR = 1.19, 95 % CI 1.12–1.26). No significance was found for SNP rs2335704. The results provided an independent support for a role in susceptibility to TB for SNP rs4331426. However, it also indicated that direct predisposition element to TB and the association effects may vary across ethnic groups.     

The HLA system of the Uzbek population in the Ferghana Valley. HLA antigens, genes and haplotypes of the Uzbek population in relation to its ethnogenesis

Pecularities of distribution of 40 HLA antigens within the Uzbek population of the Ferghana Valley have been studied. The frequencies of these antigens are subdivided into three main groups having frequencies characteristic of the following populations: Caucasoid population (A9, B40, Bw22 etc.); Mongoloid population (B8, B7, B12); Middle Asian population (Aw31, B13, B16, Bw35), probably. The Uzbek population contains haplotypes both of Europeoid (Aw30, B13; A3, Bw35) and Mongoloid origin (A9, B40) and, probably, of the local origin (A1, B14; A1, Bw53; Aw32, B40). The data on the HLA genetics of the Uzbeks confirm the historical, linguistic and anthropological information concerning the role of inhabitants of the Central Asia in ethnogenesis and formation of the modern Uzbek population.     

HLA polymorphisms are associated with Helicobacter pylori infected gastric cancer in a high risk population, China

Helicobacter pylori is one of the most common bacterial infections associated with an increased risk of gastric cancer, but its association with host factors, particularly polymorphisms of the immune response genes, such as human leukocyte antigen (HLA) genes, is still unclear. To investigate the role of HLA polymorphisms in the risk of gastric cancer among subjects with H. pylori infection, a case-control study involving 52 gastric cancer patients and 139 non-cancer controls was conducted in Linqu County, China, an area with a high incidence of gastric cancer. Polymorphisms of HLA class I and class II alleles were determined by PCR with sequence-specific primers (PCR-SSP). The information about H. pylori infection was obtained from previous records. Among 48 class I and 19 class II HLA alleles detected in this study, two alleles, CW*03 and DRB1*01, were found to be distributed significantly differently between patients and controls [odds ratio(OR)=1.95, 95% confidence interval (CI)=1.13–3.35, P=0.017 and OR=4.39, 95% CI=1.39–13.84, P=0.012, respectively). The OR of gastric cancer risk in individuals carrying CW*03/CW*03 or CW*03/CW*N was 2.06, 95% CI=1.05–4.02, P=0.035, while the OR was 3.49, 95% CI=1.0–12.4, P=0.04 for DRB1*01/DRB1*01 or DRB1*01/DRB1*N carriers. The analysis of the interaction between H. pylori infection and HLA risk genotypes of CW*03 or DRB1*01 revealed that the effect of CW*03 and DRB1*01 genotypes on gastric cancer risk was manifested stronger in H. pylori-positive individuals (OR=5.30, 95% CI=1.73–16.29, P=0.004 and OR=13.38, 95% CI=2.52–70.98, P=0.002, respectively) than in H. pylori-negative ones (OR=1.25, 95% CI=0.25–6.12, P=0.785 and OR=2.26, 95% CI=0.18–28.88, P=0.531, respectively). The combined effect of the two risk HLA genotypes on gastric cancer risk was also analysed. The result showed that the individuals carrying both the CW*03 and DRB1*01 alleles could only be found in cancer patients (5/52), and not in controls (0/139), further suggesting that CW*03 and DRB1*01 are risk alleles advancing the progression of tumorigenesis. These observations demonstrate that host HLA genotypes may play an important role in the risk of gastric cancer, especially among persons with H. pylori infection.     

Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR]?= 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.     

Association study of promoter polymorphisms in the CETP gene with longevity in the Han Chinese population

The cholesteryl ester transfer protein (CETP), which is involved in the regulation of reverse cholesterol transport and metabolism of high-density lipoprotein cholesterol, has been proposed as a candidate gene for human longevity. SNPs in the promoter region of the CETP gene is likely important in regulation of the expression of the CETP gene. To explore the potential effects of the promoter polymorphisms in the CETP gene on longevity, we investigated the promoter polymorphisms in a sample of long-lived (≥90 years old) Han Chinese collected from Southwestern China (N = 380). By resequencing 934 bp of the promoter region, genotypes of four SNPs (?573A/G, ?629A/C, ?971A/G, ?1046T/C) were examined in this sample. However, no association could be confirmed between longevity and these SNPs or haplotypes inferred from them. A novel rare variant ?573A/G was found and was found in heterozygote state only in five persons in the Longevity group. But it was not statistically significant (p = 0.075). We also examined this novel polymorphism ?573A/G in another Han Chinese sample from Yunnan province, and it was not associated with longevity. The results from both samples suggest that there is likely no association of the CETP gene promoter polymorphisms with longevity, at least among Han Chinese.     

HLA class I polymorphism in the Albanian population

The HLA class I polymorphism was studied in a sample of the Albanian population. Ninety-three unrelated healthy Albanians were typed for HLA-A, -B and -Cw antigens by standard microlyphocytotoxicity test. The antigens with the highest frequencies were: HLA-A2 (34.4%), A3 (14.5%) and A1 (12.4%); B51 (19.3%), B35 (12.4%) and B18 (10.2%); Cw4 (16.2%), Cw7 (16.2%) and Cw6 (10.8%). The HLA haplotypes with high frequency in Albanians included A2-B51 (4.3%), A2-B18 (2.4%), A2-B35 (2.4%), Cw4-B35 (7.6%), and Cw7-B18 (6.5%), which are not significantly different from the other neighboring populations. Low frequency of HLA-A1-B8 haplotype (1.1%) is noted in the Albanian population. The frequency of HLA-B27 antigen (1.1%) is one of the lowest frequencies observed in Caucasians. Such results are important in studies of HLA-A1-B8, HLA-B27 and disease associations. These findings should be also useful in understanding the origin of Albanians, representing a base for future studies about HLA polymorphism in the Albanian population.     

IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population

Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case–control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including ?1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary TB subgroup suggests a sufficient IFN-γ expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.     

HLA supratypes in an Italian population

A supratype analysis of a North Italian population was performed, using 16 polymorphisms in the HLA region spanning the HLA-A-DP segment. Fourteen supratypes were identified, mostly corresponding to those found in other Caucasiod populations. The degree of their conservation both within the B-DR/DQ region and in the regions telomeric and centromeric from HLA-A and DP was evaluated and linkage disequilibria among several DR and DP alleles were identified. Notably, the degree of association with DP increased when the DR marker was part of a conserved B-DR/DQ supratype. These data are relevant to the definition of the genetic structure of the population and to the prediction of probabilities of histocompatibility matching between unrelated individuals.     

Association between XPG polymorphisms and stomach cancer susceptibility in a Chinese population

Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3′ terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital‐based case–control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03–1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13–2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non‐cardia stomach cancer. Further combined analysis indicated men, smokers, or non‐drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.