Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

CONTEXT: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. OBJECTIVE: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. METHODS: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. RESULTS: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). CONCLUSIONS: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Transferrin receptor levels and its rare variant are associated with human obesity.

AIM: Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. METHODS: To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. RESULTS: TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. CONCLUSIONS: Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0-10.5% [53-91 mmol/mol]) were randomly assigned to receive 3 mg mazdutide (n = 51), 4.5 mg mazdutide (n = 49), 6 mg mazdutide (n = 49), 1.5 mg open-label dulaglutide (n = 50), or placebo (n = 51) subcutaneously for 20 weeks. The primary outcome was change in HbA1c from baseline to week 20. RESULTS: Mean changes in HbA1c from baseline to week 20 ranged from -1.41% to -1.67% with mazdutide (-1.35% with dulaglutide and 0.03% with placebo; all P < 0.0001 vs. placebo). Mean percent changes in body weight from baseline to week 20 were dose dependent and up to -7.1% with mazdutide (-2.7% with dulaglutide and -1.4% with placebo). At week 20, participants receiving mazdutide were more likely to achieve HbA1c targets of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) and body weight loss from baseline of ≥5% and ≥10% compared with placebo-treated participants. The most common adverse events with mazdutide included diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10% [8% with placebo]). CONCLUSIONS: In Chinese patients with type 2 diabetes, mazdutide dosed up to 6 mg was generally safe and demonstrated clinically meaningful HbA1c and body weight reductions.

Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic ß cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

Antibiotic Azithromycin inhibits brown/beige fat functionality and promotes obesity in human and rodents.

Obesity, a metabolic disease caused by multiple factors, has become a global health problem. In addition to nutrient intake and sedentary lifestyle, environmental pollutants exposure has been shown to be involved in obesity epidemics. Antibiotics, a new type of environmental pollutant, have been widely used in animal husbandry, aquaculture and microorganism. However, the effects of antibiotics exposure on fat metabolism and metabolic diseases are largely unknown. Methods: We screened major types of antibiotics to examine their effects on the differentiation capacity and thermogenic functionality of brown and beige adipocytes, and found that azithromycin, one major kind of macrolide antibiotics suppressed brown and beige adipocyte functionality. We thus examined azithromycin accretion in adipose tissues of obese patients that correlates with BMI by high performance liquid chromatography-tandem mass spectrometry and systematically explore the influences of azithromycin on adiposity and metabolic performance in mice under high diet. Results: Azithromycin (macrolides) inhibits the mitochondrial and thermogenic gene programs of brown and beige adipocytes, thus disrupting their mitochondrial function and thermogenic response. Consistently, azithromycin treatment are more prone to diet-induced obesity in mice, and this was associated with impaired energy expenditure. Importantly, azithromycin is more accumulated in adipose tissue of obese patients and correlates with BMI and body weight. Mechanistically, we found that azithromycin inhibits mitochondria respiratory complex I protein levels and increases reactive oxidative species (ROS) levels, which causes damage of mitochondrial function in brown and beige adipocytes. The deleterious effects of azithromycin can be ameliorated by antioxidant N-acetyl-L-cysteine. Conclusions: Taken together, this work highlights the possible role of azithromycin in obesity epidemic and presents strategies for safe applications of antibiotics in the future.

Associations of early-life exposure to famine with abdominal fat accumulation are independent of family history of diabetes and physical activity.

The present study aimed to investigate the association of early-life exposure to famine with abdominal fat accumulation and function and further evaluate the influence of first-degree family history of diabetes and physical activity on this association. The present work analysed parts of the REACTION study. A total of 3033 women were enrolled. Central obesity was defined as waist circumferences (W) ≥ 85 cm. Chinese visceral adiposity index (CVAI) was used to evaluate visceral adipose distribution and function. Partial correlation analysis showed BMI, W, glycated Hb and CVAI were associated with early-life exposure to famine (both P < 0·05). Logistic regression showed that the risks of overall overweight/obesity and central obesity in fetal, early-childhood, mid-childhood and late-childhood exposed subgroups were increased significantly (all P < 0·05). Compared with the non-exposed group, the BMI, W and CVAI of fetal, early- to late-childhood exposed subgroups were significantly increased both in those with or without first-degree family history of diabetes and in those classified as physically active or inactive, respectively (all P < 0·05). The associations of BMI, W and CVAI with early-life exposure to famine were independent of their associations with first-degree family history of diabetes (all P < 0·01) or physical activity status (all P < 0·001). Early-life exposure to famine contributed to abdominal fat accumulation and dysfunction, which was independent of the influence of genetic background and exercise habits. Physical activity could serve as a supplementary intervention for women with high risk of central obesity.

Inverse association between physical activity and blood glucose is independent of sex, menopause status and first-degree family history of diabetes.

AIMS/INTRODUCTION: Exercise training is a recognized strategy central to the prevention, treatment, and management of diabetes and prediabetes. The aim of the present study was to investigate the association between physical activity and blood glucose, as well as the influence of sex, menopause status and family history of diabetes. MATERIALS AND METHODS: Participants with normal weight were selected from Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, and divided into inactive (moderate-to-vigorous-intensity physical activity [MVPA] <30 min/week), low-degree (MVPA ≥30 and ≤420 min/week) and high-degree (MVPA >420 min/week) activity groups. RESULTS: A total of 2,601 individuals with an average age of 57.85 ± 8.39 years were enrolled. Multivariate anova uncovered that after adjustment for sex and menopause status, and family history of diabetes, respectively, fasting plasma glucose, 2-h plasma glucose and glycated hemoglobin A1c decreased through inactive, low-degree and high-degree activity groups (all P for trend <0.05). The association of blood glucose indexes with physical activity was independent of this association with sex and menopause status, and first-degree family history of diabetes, respectively. Multivariate linear regression analyses showed that MVPA was an independent factor associated negatively with fasting plasma glucose, 2-h plasma glucose and glycated hemoglobin A1c, respectively (all P < 0.01). CONCLUSIONS: A higher degree of physical activity was associated with lower blood glucose regardless of sex, menopause status and first-degree family history of diabetes. MVPA is a negative factor associated with blood glucose independently. Physical activity of adequate duration and intensity is strongly recommended to individuals with susceptibility to diabetes as a result of sex and family history, but without overweight/obesity.

Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms.

Ginsenosides, the major active constituents of ginseng, have been demonstrated possess anti-diabetic, anti-inflammatory effects. Ginsenoside Rb2 (Rb2) is the most abundant saponin in Panax ginseng, this study investigates the role of Rb2 in the anti-hyperglycemic mechanism of insulin-sensitive cell lines 3T3-L1 adipocytes as well as high fat diet-induced obesity mice. Glucose uptake of 3T3-L1 adipocytes was measured. The insulin signaling cascade, including insulin AKT, insulin receptor (IR) beta-subunit, IR substrate (IRS) -1, phosphatidylinositol 3-kinase (PI3K) were also examined. TNF-α-treated 3T3-L1 adipocytes were used as an insulin resistant model in which p-AKT, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF) -κB signaling cascades were examined. As an in vivo study, C57BL/6J mice were fed with a high-fat diet for 9 weeks, with or without Rb2 supplementation. Then we investigated the effects of Rb2 on glycometabolism in these high fat diet-induced obesity mice. Our results demonstrate Rb2 increases glucose uptake in 3T3-L1 adipocytes, independent of insulin receptor ß-subunit (IRß) and principally through the insulin receptor substrate (IRS)-1-phosphatidylinositol 3-kinase (PI3K)-AKT/PKB pathway. Rb2 inhibited TNF-α-induced activation of MAPK and nuclear factor (NF)-κB signaling pathway as well as the expression of inflammatory factors. In high fat diet-induced obesity mice, Rb2 attenuated fat mass and regulated insulin resistance. In mouse adipose tissue, Rb2 phosphorylation of AKT was correlated with glycometabolism. Furthermore, Rb2 attenuates insulin resistance in 3T3-L1 adipocytes, reduces fat mass, and improves insulin sensitivity in high fat diet-obesity mice.

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats.

We aim to explore effects of Ketotifen on metabolic profiles, inflammation and oxidative stress. Sprague Dawley (SD) male rats were randomly divided into normal control group (NC) and experimental groups, and experimental group rats were fed with high-sugar and fat diet for 6 weeks. Then, experimental group rats were divided into diabetes group (DM) and ketotifen treatment group (KT). KT group was given ketotifen via Intragastric for 8 weeks with the dosage of 0.09 mg/kg/d. Fasting plasma glucose (FPG) was measured using glucose oxidase-phenol amino phenazone method. Fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by enzyme-linked immunosorbent assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) were quantified by spectrophotometer method. Before Ketotifen administration, compared with NC group, DM and KT groups showed significantly high levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α and MDA, and lower levels of HDL and SOD (All p <0.05). After 4 weeks of Ketotifen administration, levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α in KT group decreased significantly, and levels of HDL and SOD elevated significantly (All p <0.05). After 8 weeks of Ketotifen administration, levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α and MDA in KT group decreased more obviously, and levels of HDL and SOD elevated significantly further (All p <0.05). Ketotifen improved metabolic profiles, and ameliorated status of inflammation and oxidative stress.

Waist-to-height ratio is an appropriate index for identifying cardiometabolic risk in Chinese individuals with normal body mass index and waist circumference.

BACKGROUND: The waist-to-height ratio (WHtR), a novel index that has been reported to correlate more strongly than body mass index (BMI) and waist circumference (WC) with cardiometabolic risk factors, has not been studied in Chinese individuals with normal body mass index and waist circumference. The present study compared the predictive power of WHtR with those of BMI and WC for such factors in non-obese Chinese, and to define optimal cutoffs of WHtR in this population. METHODS: A total of 2137 subjects aged 40-75 years were recruited. Three anthropometric indices (WHtR, BMI, and WC) were compared and the optimal cutoffs of WHtR were identified by receiver operating characteristic curve (ROC) analysis. WHtR was divided into four quartiles (WHtR-Q), and multiple linear regression analyses were used to calculate the relationship between WHtR-Q and clinical biochemical index. RESULTS: Waist-to-height ratio was more efficient than WC to identify cardiometabolic risk factors in both genders, but was only superior to BMI in females. WHtR-Q was positively correlated with fasting plasma glucose, 2-h postprandial blood glucose, and systolic blood pressure, and negatively connected with high density lipoprotein cholesterol in both genders after controlling for age, current smoking and drinking, moderate-intensity physical activity, daily sedentary time, daily screen time and menopause (only for females). The optimal cutoffs of WHtR for detecting cardiometabolic risk factors were 0.47 in males and 0.51 in females. CONCLUSION: Waist-to-height ratio might be an effective index to identify cardiometabolic risk factors in Chinese with normal BMI and WC, particularly in females.

Over-expression of AQP7 contributes to improve insulin resistance in adipocytes.

OBJECTIVE: Aquaglyceroporin 7 (AQP7) is required for efflux of glycerol from adipocytes. In this study, we aimed to analyze expression profiles of AQP7 in the different differentiation phases of adipocytes and to investigate the role of AQP7 in the insulin resistance of adipocytes. METHODS: 3T3-L1 pre-adipocyte cells were induced to be fully differentiated adipocytes and then insulin resistance was induced by Dexamethasone (DXM) or TNF-α. Adenovirus vector with over-expression AQP7 (Ad-AQP7) was constructed and transfected into adipocytes. The expression level of AQP7 and phosphorylated PKB (p-PKB) were measured. The glycerol released from adipocytes and glucose consuming rate were tested too. RESULTS: AQP7 expression was gradually up-regulated along with the differentiation processing of 3T3-L1 preadipocytes, which was consistent with the expression level of p-PKB. Dexamethasone down-regulated the expression of AQP7, p-PKB and the glycerol content in adipocytes. Over-expression of AQP7 by transfecting Ad-AQP7 to insulin resistant adipocytes restored the phosphorylation of PKB and attenuated the glycerol secretion and glucose consuming rate of adipocytes. CONCLUSIONS: AQP7 is down-regulated in adipocytes with insulin resistance. The over-expression of AQP7 contributes to improve insulin resistance in adipocytes, which is potentially correlated with the increased phosphorylation of PKB.

The A946T polymorphism in the interferon induced helicase gene does not confer susceptibility to Graves' disease in Chinese population.

Genetic susceptibility plays a major role in the etiology of Graves' disease (GD). A recent study revealed that the A946T polymorphism (rs1990760) in interferon induced helicase (IFIH1) gene was a susceptible locus for GD. A case-control study in a Chinese population was undertaken, with 261 GD patients and 206 healthy subjects, to analyze the association of A946T polymorphism in IFIH1 gene with GD. In addition, the distribution of IFIH1 genotypes was investigated in subgroups according to the onset age and the Graves' ophthalmopathy (GO). No significant differences in the allele and genotype frequencies for A946T polymorphism were found between GD patients and healthy controls (chi2 = 2.834, P = 0.242; chi2 = 1.127, P = 0.288). The genotype-phenotype correlation was not identified either. Therefore we were unable to find the association of A946T polymorphism of the IFIH1 gene with the development of GD in a Chinese population.