Meihua Dong

Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population.

Background Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes. Methodology/Principal Findings A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P<0.05) observed from 1,200 cases and 1,200 controls in the first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistently associated with type 2 diabetes in both stages (P<0.05), with combined odds ratios (ORs) ranging from 1.14 to 1.33 in the combined analysis. The most significant locus was rs7923837 [OR = 1.33, 95% confidence interval (CI): 1.21–1.47] at the 3′-flanking region of HHEX gene. SNP rs1111875 was found to be another partially independent locus (OR = 1.23, 95% CI: 1.13–1.35) in this region that was associated with type 2 diabetes risk. A cumulative effect of rs7923837 and rs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively, for type 2 diabetes (P for trend = 4.1E-10). Conclusions/Significance Our results confirm that genetic variants of the IDE-KIF11-HHEX region at 10q23.33 contribute to type 2 diabetes susceptibility and suggest that rs7923837 may represent the strongest signal related to type 2 diabetes risk in the Chinese Han population.

Incidence and mortality of female breast cancer in Jiangsu, China.

OBJECTIVES The aim of this study was to describe and analyze the incidence and mortality of female breast cancer in Jiangsu Province of China. METHODS Incidence and mortality data for female breast cancer and corresponding population statistics from eligible cancer registries in Jiangsu from 2006 to 2010 were collected and analyzed. Crude rates, age-specific rates and age-standardized rates of incidence and mortality were calculated, and annual present changes (APCs) were estimated to describe the time trends. RESULTS From 2006 to 2010, 11,013 new cases and 3,068 deaths of female breast cancer were identified in selected cancer registry areas of Jiangsu. The annual average crude incidence and age-standardized incidence by world population (ASW) were 25.2/ and 17.9/100,000 respectively. The annual average crude and ASW for mortality rates were 7.03/ and 4.81/100,000. The incidence was higher in urban areas than that in rural areas, and this was consistent in all age groups. No significant difference was observed in mortality between urban and rural areas. Two peaks were observed when looking at age-specific rates, one at 50-59 years and another at over 85 years. During the 5 years, incidence and mortality increased with APCs of 4.47% and 6.89%, respectively. Compared to the national level, Jiangsu is an area with relatively low risk of female breast cancer. CONCLUSION Breast cancer has become a main public health problem among Chinese females. More prevention and control activities should be conducted to reduce the burden of this disease, even in relatively low risk areas like Jiangsu.

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case-control study in Han Chinese

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) on chromosome 6p21.1 and 6p22.3 as type 2 diabetes (T2D) susceptibility loci in the European and Japanese populations. However, these SNPs have not been well evaluated in Chinese population. Here, we performed a case–control study with 2925 T2D cases and 3281 controls in a Chinese population. We used TaqMan OpenArray and Sequenom MassARRAY to genotype the four SNPs (rs4712523, rs7756992, rs4712524 and rs6931514) in CDKAL1 (cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1) at 6p22.3 and one SNP (rs9472138) near vascular endothelial growth factor A (VEGFA) at 6p21.1. All the five SNPs were significantly associated with T2D risk with overall effects (odds ratio, OR) from 1.19 to 1.29 in the additive genetic model (rs6931514: OR=1.29, 95% confidence intervals (95% CI)=1.19–1.39, P=5.6 × 10−10; rs7756992: OR=1.23, 95% CI=1.15–1.32, P=1.2 × 10−8; rs4712523: OR=1.25, 95% CI=1.15–1.35, P=3.8 × 10−8; rs4712524: OR=1.24, 95% CI=1.15–1.35, P=6.8 × 10−8; rs9472138: OR=1.19, 95% CI=1.05–1.34, P=006). Conditional analysis identified two independent signals (rs6931514 at 6p22.3 and rs9472138 at 6p21.1) that were significantly associated with T2D. Compared with the wild homozygote of rs6931514 and rs9472138, subjects with variant alleles of the two SNPs had increased risk for T2D susceptibility in a dose-response manner (Ptrend=7.4 × 10−12). Our findings indicated that genetic variants of CDKAL1 and VEGFA on chromosome 6 may contribute to T2D risk in Chinese population, especially for rs9472138 at 6p21.1 identified for the first time to significantly increase the T2D risk in Chinese individuals.

Cumulative effect and predictive value of genetic variants associated with type 2 diabetes in Han Chinese: a case-control study.

Background Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We have previously confirmed the associations of genetic variants in HHEX, CDKAL1, VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes in Han Chinese are largely unknown. Methodology/Principal Findings We conducted a two-stage case-control study consisting of 2,925 cases and 3,281controls to examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio (OR) = 1.41, P = 9.91 × 10–16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34 × 10–10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 × 10-4 for rs1552224) and SLC30A8 (OR = 1.19, P = 1.43 × 10-5 for rs13266634). We further evaluated the cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or more risk alleles had a nearly 4-fold increased risk for developing type 2 diabetes compared with those carrying less than 6 risk alleles [adjusted OR = 3.68, 95% confidence interval (CI): 2.76–4.91]. Adding the genetic factors to clinical factors slightly improved the prediction of type 2 diabetes, with the area under the receiver operating characteristic curve increasing from 0.76 to 0.78. However, the difference was statistically significant (P < 0.0001). Conclusions/Significance We confirmed associations of SNPs in KCNQ1, CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The utilization of genetic information may improve the accuracy of risk prediction in combination with clinical characteristics for type 2 diabetes.

Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese

BackgroundGenome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case–control study with 2,925 T2D patients and 3,281 controls in Han Chinese.ResultsLogistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19).ConclusionsOur findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.

Joint effect of CENTD2 and KCNQ1 polymorphisms on the risk of type 2 diabetes mellitus among Chinese Han population

Genome-wide association studies (GWAS) in populations of European ancestry have identified nine single nuclear polymorphisms (SNP) on chromosome 11 related to type 2 diabetes (T2D) susceptibility. Herein, we further evaluate the association of these SNPs and T2D in a Chinese Han population. We performed a case-control study of 2925 T2D cases and 3281 controls to evaluate the association of five SNPs of KCNJ11, MTNR1B, CENTD2 and LOC387761 and T2D in addition to the previously reported four SNPs of KCNQ1. Multiple logistic regression was used to evaluate SNPs effect by adjustment for confounding factor age, sex and BMI. In the first stage, SNPs rs1552224 at CENTD2 were significantly associated with T2D and the association was statistically significant in the whole study population (P = 0.001) although it was not replicated in the second stage. rs1552224 and rs2237897 of KCNQ1 showed significant joint effect on T2D and there was a significant decreased risk of T2D with the number increase of risk alleles (P for trend = 3.81 × 10(-17)). Compared to those without carrying any risk allele, individuals carrying one, two, and three or four risk alleles had a 30.7%, 44.8% and 62.0% decreased risk for developing T2D, respectively. Our finding suggests that genetic variant rs1552224 of CENTD2 on chromosome 11 contributes to an independent effect as well as joint cumulative effect with rs2237897 of KCNQ1 on the risk of T2D in Chinese Han population, and further functional research would be warranted.

Genetic variation in the LMP/TAP gene and outcomes of hepatitis B virus infection in the Chinese population.

Genetic polymorphisms of the LMP/TAP gene coded by the HLA-II region may be associated with outcomes of HBV infection. We conducted a case-control study to test the hypothesis, including a persistent group of 155 patients with chronic hepatitis B and 36 healthy carriers, a recovered group of 165 individuals spontaneously recovered from HBV infection, and an uninfected group of 278 healthy normal controls. Genotypes of eight polymorphisms of the LMP/TAP gene were analysed by PCR-RFLP. A logistic regression model was used to analyse statistical differences in polymorphisms or haplotypes in different groups. Of the eight polymorphisms, two (TAP1 codon 637 and LMP7 codon 145) were observed to have statistically significant association with outcomes of HBV infection (P<0·05). The two-locus haplotype constructed with two such polymorphisms was analysed. The frequencies of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were found to be increased significantly in the persistent group, compared to healthy controls (OR 2·26, 95% CI 1·62-3·15, P<0·001; OR 2·37, 95% CI 1·69-3·32, P<0·001; OR 4·38, 95% CI 1·78-10·77, P=0·001, respectively). The prevalence of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were also significantly higher in the persistent infectious group than in the recovered group (OR 2·68, 95% CI 1·81-3·98, P<0·001; OR 2·40, 95% CI 1·62-3·55, P<0·001; OR 3·03, 95% CI 1·22-7·55, P=0·017, respectively). These findings indicated that genetic polymorphisms of the LMP/TAP gene might be an important factor in determining the outcome of HBV infection.

A Tailored Target Intervention on Influence Factors of Quality of Life in Chinese Patients with Hypertension

Studies suggested that hypertension was associated with impaired health-related quality of life and it is important to find a proper and feasible management of hypertension in the community. This study evaluates the effect of a tailored target intervention on influence factors of quality of life in Chinese patients with hypertension. A cross-sectional survey was carried out to investigate 644 patients with hypertension by using the Chinese version of the short form-36, and 195 patients were screened out to participate in the tailored target intervention. Multivariate linear regression analyses showed that age, gender, educational level, high intake of fried food, household income, attitude, knowledge, blood pressure, symptoms, serious events during the past year, duration of hypertension, and number of taking anti-hypertensive medicine were significantly correlated with quality of life. Grade-based management by community physicians and physical exercise had a positive effect on quality of life. After the 6-month intervention, the control rate of hypertension was increased from 32.0% to 39.4%, and the mean systolic and diastolic blood pressure values were significantly decreased to 137.2 and 85.7 mmHg vs. 140.9 and 87.6  mmHg at baseline, respectively. The intervention program resulted in overall improvement on total score of quality of life and mean scores of all the domains except social functioning in patients with hypertension. In view of the influence factors of quality of life, taking the tailored target intervention could not only improve the quality of life of hypertensive patients, but also effectively increase the control rate of hypertension.

TGFBR1 tagging SNPs and gastric cancer susceptibility: a two-stage case-control study in Chinese population.

The transforming growth factor (TGF)‐β is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF‐β receptor type I (TGFβR1) may be a modifier of cancer risk by constitutively decreasing the TGF‐β inhibitory signals during early tumorigenesis and increasing the TGF‐β signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two‐stage case–control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P = 3.35 × 10−3 for rs6478974 AT vs. TT and P = 0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P = 0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14–1.63 for rs6478974 AT/AA vs. TT; adjusted OR = 1.26, 95% CI: 1.05–1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR = 1.23, 95% CI: 1.08–1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han‐Chinese population.

The association of dietary pattern and breast cancer in Jiangsu, China : A population-based case-control study

This study aims to examine the association of breast cancer with dietary patterns among Chinese women. A population-based case-control study was conducted in Jiangsu, China. Newly diagnosed primary breast cancer patients were recruited as cases (n = 818). Controls (n = 935), selected from the general population, were frequency matched to cases. A validated food frequency questionnaire was used to assess dietary intake. Dietary patterns were identified by factor analysis and multivariable odds ratios (OR) and 95% confidence intervals (CI) were estimated. Four dietary patterns were identified: salty, vegetarian, sweet and traditional Chinese. The traditional Chinese pattern was found to be robustly associated with a lower risk of breast cancer among both pre- and post-menopausal women (4th vs. 1st quartile: OR for pre- and post-menopausal women was 0.47 and 0.68, respectively). Women with high factor scores of the sweet pattern also showed a decreased risk of breast cancer (4th vs. 1st quartile: OR for pre- and post-menopausal women was 0.47 and 0.68, respectively). No marked association was observed between a vegetarian pattern or a salty pattern and breast cancer. These findings indicate that dietary patterns of the traditional Chinese and the sweet may favorably associate with the risk of breast cancer among Chinese women.