Xiaohong Shi

The Gly482Ser variant of the PPARGC1 gene is associated with Type 2 diabetes mellitus in northern Chinese, especially men

Aims  To investigate the prevalence of the Gly482Ser polymorphism of the PPARGC1 gene in a northern Chinese population and to clarify the susceptibility of individuals with the Gly482Ser polymorphism to insulin resistance and related diseases.

Association between APOC1 Polymorphism and Alzheimer’s Disease: A Case-Control Study and Meta-Analysis

Background Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. Methods To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. Results Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ2 = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01). Conclusions The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.

Association study between late-onset Alzheimer's disease and the transferrin gene polymorphisms in Chinese.

To investigate the possible involvement of the transferrin (TF) gene polymorphism in the manifestation of Alzheimers disease (AD), we analyzed the TF and apolipoprotein E (APOE) genotypes of 67 sporadic late-onset AD patients and 131 normal elderly controls in the Chinese population. Our data showed that the TF C1 homozygosity carriers had an increased risk of AD in subjects > or =75 years of age, showing that homozygosity for the TF C1 allele was associated with an approximately three-fold increased risk (OR=3.57, 95% CI, 1.24-10.27, P=0.014). No synergic effects were found between the APOE epsilon 4 allele and TF gene polymorphisms.

Trans-Ethnical Shift of the Risk Genotype in the CETP I405V with Longevity: A Chinese Case-Control Study and Meta-Analysis

Background The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity. Methods We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification. Results Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive=0.008; P dominant=0.008, ORdominant=0.673; P recessive=0.017, ORrecessive=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans. Conclusion Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.

Risk Loci on Chromosome 8q24 are Associated With Prostate Cancer in Northern Chinese Men

PURPOSE Genome-wide association studies have identified several genetic variants at 8q24 that are strongly associated with prostate cancer risk in populations of European, American and Japanese ancestry. We investigated the contribution of these prostate cancer risk variants in the Chinese population. MATERIALS AND METHODS We evaluated the association of 14 single nucleotide polymorphisms at 8q24 with prostate cancer risk using high resolution melting curve combined gene sequencing methods in case-control groups, including 265 cases and 288 controls. We explored the association between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score and tumor stage) and risk loci in our study to infer their impact on aggressive prostate cancer. RESULTS Four of the 14 single nucleotide polymorphisms were associated with prostate cancer risk, including rs16901966 (OR 1.343, 95% CI 1.029-1.754, p = 0.030), rs1447295 (OR 1.499, 95% CI 1.109-2.027, p = 0.008), rs11986220 (OR 1.589, 95% CI 1.160-2.178, p = 0.004) and rs10090154 (OR 1.571, 95% CI 1.146-2.154, p = 0.005). Haplotype based association analysis of the risk alleles revealed significant differences between cases and controls. The risk alleles of rs16901966, rs1447295, rs11986220 and rs10090154 were associated with age at diagnosis and tumor stage compared with controls while rs16901966 was associated with aggressive prostate cancer (OR 1.538, 95% CI 1.076-2.099, p = 0.018). CONCLUSIONS For northern Chinese men rs16901966, rs1447295, rs11986220 and rs10090154 at 8q24 (region 1, region 2) are associated with prostate cancer and prostate cancer related clinical covariates.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

BACKGROUND/AIM Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. METHODS Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. RESULTS Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). CONCLUSION Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

The haplotype identified in LEPR gene is associated with type 2 diabetes mellitus in Northern Chinese

Leptin receptor (LEPR) plays an important physiological role in energy metabolism. The study addressed the relationship between leptin receptor gene variations and type 2 diabetes mellitus (T2DM). Three single nucleotide polymorphisms (SNPs) of LEPR gene, Arg109Lys (A/G), Asn656Lys (C/G) and Pro1019Pro (C/T) were detected in a northern population in China. Totally, 317 patients with T2DM and 282 healthy controls were recruited randomly from urban communities in Harbin area in the Northeast of China. All polymorphisms were genotyped by Sequenom SNP detection system in both case and control groups. Linkage disequilibria analysis showed moderate linkage disequilibria between the pair-wise SNPs for all three SNPs. Then, we identified the haplotype covering the three SNPs (AGC) with higher risk of T2DM (OR=1.69 (1.09-2.61)), and showed that there existed significant difference between cases and controls (9.8% vs. 6.0%, P=0.02). We also observed significant difference in frequencies of the heterozygous haplotype combination (GGT/AGC), that is 17.0% vs. 8.2% in cases and controls, respectively (P=0.001). It further supported the evidence that the haplotype (AGC) was associated with T2DM. So, AGC haplotype in LEPR gene could be a risk factor associated with T2DM in Northern Chinese.

Haptoglobin 2-2 Genotype Is Associated with Increased Risk of Type 2 Diabetes Mellitus in Northern Chinese

The aim of this study was to investigate the association between haptoglobin (Hp) gene polymorphism and occurrence of type 2 diabetes mellitus (T2DM) in a northern Chinese population. We studied the association of the Hp gene polymorphism with T2DM in 584 unrelated T2DM patients and 690 control subjects with normal glucose tolerance among northern Chinese. The patients were diagnosed in accordance with the guidelines of the American Diabetes Association. The clinical characteristics of the study population were recorded, and the Hp genotype was determined. The frequencies of the genotypes in the group of T2DM patients and the controls were as follows: Hp2-2, 51.7% and 44.1%; Hp2-1, 39.7% and 45.1%; and Hp1-1, 8.6% and 10.9%, respectively. There was significant difference for the genotypic and allelic distribution between the two groups (p=0.021 and p=0.007, respectively). Even after readjusting for the confounding effects of age, gender, and body mass index, a significant effect of genotypes on T2DM was still found in the recessive model for the Hp2 allele tested (p=0.002). Those who had the Hp2-2 genotype had a significantly higher risk for T2DM than those with other genotypes (odds ratio=1.441, 95% confidence interval=1.143-1.817). The results showed that the Hp2-2 genotype is associated with increased risk of T2DM in the northern Chinese Han population.

The ENPP1 K121Q polymorphism is not associated with type 2 diabetes in northern Chinese

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to insulin resistance, type 2 diabetes, and obesity, and conflicting results were observed in various populations. The purpose of the present study was to investigate the prevalence of K121Q polymorphism of ENPP1 gene and to clarify whether this polymorphism is associated with type 2 diabetes susceptibility in northern Chinese population. We studied the association of the ENPP1 K121Q polymorphism with type 2 diabetes (T2D) in 639 unrelated patients and 885 control subjects with normal glucose tolerance of northern China. The patients were diagnosed in accordance with the guidelines of the American Diabetes Association (ADA). Genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. The distribution of KK, KQ, and QQ genotypes among patients was 79.5, 19.2, and 1.3%, similar to that of the control group (79.2, 20.1, and 0.7%). After readjusting for the confounding effects of age, gender, and BMI, no significant effect of genotypes on T2D was found for any of the genetic models tested (recessive model, dominant model, or additive model). All clinical characteristics tested were similar among the different genotypes, and no significant associations were observed both in T2D patients and in controls. When subgroup analyses of T2D patients and non-diabetic controls were stratified according to BMI and waist circumference, the variant was still not associated with T2D. The results showed that the ENPP1 K121Q polymorphism is not associated with genetic susceptibility of type 2 diabetes in the northern Chinese population.

Identification of susceptibility variants in ADIPOR1 gene associated with type 2 diabetes, coronary artery disease and the comorbidity of type 2 diabetes and coronary artery disease.

Objective Adiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the “common soil” hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population. Methods Our multi-disease comparison study enrolled 657 subjects, including 165 with T2D, 173 with CAD, 174 with both T2D and CAD (T2D+CAD), and 145 local healthy controls. Six ADIPOR1 single nucleotide polymorphisms (SNPs) were genotyped and their association with disease risk was analyzed. Results Multi-case-control comparison identified two ADIPOR1 variants: rs3737884-G, which was simultaneously associated with an increased risk of T2D, CAD, and T2D+CAD (P-value range, 9.80×10−5−6.30×10−4; odds ratio (OR) range: 1.96–2.42) and 16850797-C, which was separately associated with T2D and T2D+CAD (P-value range: 0.007–0.014; OR range: 1.71–1.77). The risk genotypes of both rs3737884 and 16850797 were consistently associated with common metabolic phenotypes in all three diseases (P-value range: 4.81×10−42−0.001). We observed an increase in the genetic dose-dependent cumulative risk with increasing risk allele numbers in T2D, CAD and T2D+CAD (P trend from 1.35×10−5−0.002). Conclusions Our results suggest that ADIPOR1 risk polymorphisms are a strong candidate for the “common soil” hypothesis and could partially contribute to disease susceptibility to T2D, CAD, and T2D with CAD in the Northern Han Chinese population.