Common Variation Neighbouring Micro-RNA 22 Is Associated with Increased Left Ventricular Mass

Aims

Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22), has been implicated in cardiac hypertrophy and heart failure in animal models. We thus investigated the relationship between common genetic polymorphisms surrounding miR-22 and left ventricular mass in a family-based association study.

Methods and Results

We studied a cohort of 255 families comprising 1,425 individuals ascertained via a hypertensive proband. Ten single nucleotide polymorphisms which together tagged common genetic variation surrounding the miR-22 gene were genotyped. There was evidence of association between the rs7223247 polymorphism, which lies within the 3′UTR of a gene of unknown function, TLCD2, immediately downstream from miR-22, and left ventricular mass determined by Sokolow-Lyon voltage (Bonferroni corrected p-value = 0.038). The T allele at rs7223247 was associated with an 0.272 standard deviation higher Sokolow-Lyon voltage. Genotype was responsible for ∼1% of the population variability in LVM.

Conclusions

Genotype at the rs7223247 polymorphism affects left ventricular mass determined by Sokolow-Lyon voltage. The neighbouring genes miR-22 and TLCD2 are strong candidates to account for this observation.     

Genetic Variation in the NOC Gene Is Associated with Body Mass Index in Chinese Subjects

Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including CLOCK, BMAL1(ARNTL), PER1, PER2, CRY1, CRY2, CSNK1E,, and NOC(CCRN4L) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan. Their associations with metabolic phenotypes were analyzed. We found that genetic variation in the NOC gene, rs9684900 was associated with body mass index (BMI) (P = 0.0016, Bonferroni corrected P = 0.032). Another variant, rs135764 in the CSNK1E gene was associated with fasting glucose (P = 0.0023, Bonferroni corrected P = 0.046). These associations were consistent in both Taipei and Yunlin populations. Significant epistatic and joint effects between SNPs on BMI and related phenotypes were observed. Furthermore, NOC mRNA levels in human abdominal adipose tissue were significantly increased in obese subjects compared to non-obese controls.

Conclusion

Genetic variation in the NOC gene is associated with BMI in Chinese subjects.     

Early Life Predictors of Increased Body Mass Index among Indigenous Australian Children

Aboriginal and Torres Strait Islander Australians are more likely than non-Indigenous Australians to be obese and experience chronic disease in adulthood—conditions linked to being overweight in childhood. Birthweight and prenatal exposures are associated with increased Body Mass Index (BMI) in other populations, but the relationship is unclear for Indigenous children. The Longitudinal Study of Indigenous Children is an ongoing cohort study of up to 1,759 children across Australia. We used a multilevel model to examine the association between children’s birthweight and BMI z-score in 2011, at age 3-9 years, adjusted for sociodemographic and maternal factors. Complete data were available for 682 of the 1,264 children participating in the 2011 survey; we repeated the analyses in the full sample with BMI recorded (n=1,152) after multilevel multiple imputation. One in ten children were born large for gestational age, and 17% were born small for gestational age. Increasing birthweight predicted increasing BMI; a 1-unit increase in birthweight z-score was associated with a 0.22-unit (95% CI:0.13, 0.31) increase in childhood BMI z-score. Maternal smoking during pregnancy was associated with a significant increase (0.25; 95% CI:0.05, 0.45) in BMI z-score. The multiple imputation analysis indicated that our findings were not distorted by biases in the missing data. High birthweight may be a risk indicator for overweight and obesity among Indigenous children. National targets to reduce the incidence of low birthweight which measure progress by an increase in the population’s average birthweight may be ignoring a significant health risk; both ends of the spectrum must be considered. Interventions to improve maternal health during pregnancy are the first step to decreasing the prevalence of high BMI among the next generation of Indigenous children.     

Body Mass Index Is Associated with Physical Performance in Suburb-Dwelling Older Chinese: A Cross-Sectional Study

Background

Physical performance is reported to have various beneficial effects on human health, especially in older individuals. Although such effects are associated with body mass index (BMI), the relationship between BMI and physical performance has not been clarified.

Design

We conducted a cross-sectional study of 966 suburb-dwelling Tianjin individuals aged ≥ 60 years (average age 67.5±6.02, men 435, women 531). Mobility, balance, and muscle strength were assessed by walking speed, timed up-and-go test (TUGT), and grip strength, respectively. The subjects were categorized into three groups based on BMI (kg/m²) as follows: normal weight, 18.5 ≤ BMI ≤ 23.9; overweight, 24.0 ≤ BMI ≤ 27.9; and obese, BMI ≥ 28.0.

Result

After adjusting for all other variables, relative grip strength decreased when BMI increased in both men and women (P for trend <0.001 and <0.001, respectively). BMI may be negatively associated with TUGT performance in the women only. There was no apparent association between walking speed and BMI in either sex, but after adjusting for age, walking speed was faster when BMI increased in women (P for trend= 0.0162).

Conclusion

This study suggests that in older individuals, higher BMI is associated with poor muscle strength in both sexes.     

Body Mass Index Is Associated with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Background

Prior work suggested that patients with inflammatory bowel diseases (IBD) have lower body mass index (BMI) than controls and patients with lower BMI have more serious complications.

Goal

The study was aimed to find relationship between BMI in patients with and without IBD, investigate effects of medicine therapy and disease stages on patients’ BMI.

Methods

Potentially eligible studies were identified through searching PubMed, Cochrane and Embase databases. Outcome measurements of mean BMI and the number of patients from each study were pooled by a random-effect model. Publication bias test, sensitivity analysis and subgroup analysis were conducted.

Results

A total of 24 studies containing 1442 patients and 2059 controls were included. Main results were as follows: (1) BMI in Crohn’s disease (CD) patients was lower than that in health controls (-1.88, 95% CI -2.77 to -1.00, P< 0.001); (2) Medical therapy significantly improved BMI of CD patients (with therapy: -1.58, -3.33 to 0.16; without: -2.09, 95% CI -3.21 to -0.98) while on the contrary not significantly improving BMI of UC patients (with therapy: -0.24, 95% CI -3.68 to 3.20; without: -1.34, 95% CI -2.87 to 0.20, P = 0.57); (3) Both CD and UC patients in active phase showed significantly greater BMI difference compared with controls than those in remission (CD patients: remission: -2.25, 95% CI -3.38 to -1.11; active phase: -4.25, 95% CI -5.58 to -2.92, P = 0.03; UC patients: remission: 0.4, 95% CI -2.05 to 2.84; active phase: -5.38, -6.78 to -3.97, P = 0.001).

Conclusions

BMI is lower in CD patients; medical therapy couldn’t improve BMI of IBD patients; the state of disease affects BMI of CD patients and UC patients.     

Work‐Related Physical Activity Is Not Associated with Body Mass Index and Obesity

Objective: To analyze the association of work‐related physical activity (WRPA) and leisure‐time physical activity (LTPA) with body mass index (BMI) and obesity in the Spanish adult population aged 20 to 60 years. Research Methods and Procedures: The data were taken from the 1993 Spanish National Health Survey. We analyzed a sample of 12,044 men and women representative of the Spanish population aged 20 to 60 years. BMI and frequency of obesity (BMI ≥ 30 kg/m²) were obtained from self‐reported weight and height. Multiple linear regression and logistic regression models were constructed, adjusting for the main confounding factors. WRPA and LTPA were measured by two questions to classify subjects into four categories of physical activity. Results: Neither mean BMI nor percentage of obesity varied significantly (p > 0.05) by WRPA. Mean BMI was significantly higher (p < 0.01) in those who were inactive in their leisure time (25.90 kg/m² in men and 24.43 kg/m² in women) than in those who reported vigorous activity (24.42 kg/m² and 22.97 kg/m² in men and women, respectively). The odds ration (OR) for obesity decreased with increasing level of LTPA in both men (OR of 0.64 for vigorous activity) and women (OR = 0.68), showing a statistically significant dose‐response relation in both men (for linear trend, p = 0.0021) and women (p = 0.0245). Discussion: These results raise questions about the association between WRPA and obesity and suggest the need to reexamine models of the obesity epidemic that point to automation of the workplace as one of the major explanatory factors.     

Urinary Phthalate Metabolites Are Associated with Body Mass Index and Waist Circumference in Chinese School Children

Background

Lab studies have suggested that ubiquitous phthalate exposures are related to obesity, but relevant epidemiological studies are scarce, especially for children.

Objective

To investigate the association of phthalate exposures with body mass index (BMI) and waist circumference (WC) in Chinese school children.

Methods

A cross-sectional study was conducted in three primary and three middle schools randomly selected from Changning District of Shanghai City of China in 2011–2012. According to the physical examination data in October, 2011, 124 normal weight, 53 overweight, and 82 obese students 8–15 years of age were randomly chosen from these schools on the basis of BMI-based age- and sex-specific criterion. First morning urine was collected in January, 2012, and fourteen urine phthalate metabolites (free plus conjugated) were determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Multiple linear regression was used to explore the associations between naturally log-transformed urine phthalate metabolites and BMI or WC.

Results

The urine specific gravity-corrected concentrations of nine urine phthalate metabolites and five molar sums were positively associated with BMI or WC in Chinese school children after adjustment for age and sex. However, when other urine phthalate metabolites were included in the models together with age and sex as covariables, most of these significant associations disappeared except for mono (2-ethylhexyl) phthalate (MEHP) and monoethyl phthalate (MEP). Additionally, some associations showed sex- or age-specific differences.

Conclusions

Some phthalate exposures were associated with BMI or WC in Chinese school children. Given the cross-sectional nature of this study and lack of some important obesity-related covariables, further studies are needed to confirm the associations.     

Body Mass Index Is Better than Other Anthropometric Indices for Identifying Dyslipidemia in Chinese Children with Obesity

Background

Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are used in screening and predicting obesity in adults. However, the best identifier of metabolic complications in children with obesity remains unclear. This study evaluated lipid profile distribution and investigated the best anthropometric parameter in association with lipid disorders in children with obesity.

Methods

A total of 2243 school children aged 7–17 years were enrolled in Guangzhou, China, in 2014. The anthropometric indices and lipid profiles were measured. Dyslipidemia was defined according to the US Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The association between anthropometry (BMI, WC, and WHR) and lipid profile values was examined using chi-square analysis and discriminant function analysis. Information about demography, physical activity, and dietary intake was provided by the participant children and their parents.

Results

Children aged 10–14 and 15–17 years old generally had higher triglyceride values but lower median concentration of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with children aged 7–9 years old (all P < 0.001). These lipid parameters fluctuated in children aged 10–14 years old. The combination of age groups, BMI, WC and WHR achieved 65.1% accuracy in determining dyslipidemic disorders. BMI correctly identified 77% of the total dyslipidemic disorders in obese children, which was higher than that by WHR (70.8%) (P< 0.05).

Conclusion

The distribution of lipid profiles in Chinese children differed between younger and older age groups, and the tendency of these lipid levels remarkably fluctuated during 10 to 14 years old. BMI had better practical utility in identifying dyslipidemia among school-aged children with obesity compared with other anthropometric measures.     

Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

Objective

Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infected subjects are more insulin sensitive than STH-uninfected subjects.

Design

We performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.

Methods

From 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m²), waist-to-hip ratio (WHR), fasting blood glucose (FBG, mmol/L), insulin (pmol/L), high sensitive C-reactive protein (ng/ml) and Immunoglobulin E (IU/ml). The homeostatic model assessment for insulin resistance (HOMAIR) was calculated and regression models were used to assess the association between STH infection status and insulin resistance.

Results

424 (66%) participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m², p value = 0.03) and lower HOMAIR (0.97 vs 0.81, p value = 0.05). In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01). This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07).

Conclusion

STH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.     

Low Body Weight in Females Is a Risk Factor for Increased Tenofovir Exposure and Drug-Related Adverse Events

Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight<50 kg had significantly higher plasma tenofovir concentrations than those weighting >50 Kg (160±93 vs.71±52 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications.     

Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES

Background

Triclosan—a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies—has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.

Methods

We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003–2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures—either presence vs. absence or quartiles of triclosan—we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.

Results

Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.

Conclusions

Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.     

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients

Objective

Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients.

Methods

This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient’s demographic characteristics as well as clinical and laboratory measurements were collected.

Results

Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4–120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality.

Conclusion

Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality.     

Vitamin D Insufficiency Is Common in Ugandan Children and Is Associated with Severe Malaria

Vitamin D plays an increasingly recognized role in the innate and adaptive immune response to infection. Based on demonstrated roles in up-regulating innate immunity, decreasing inflammation, and reducing the severity of disease in illnesses such as tuberculosis and influenza, we hypothesized that poor vitamin D status would be associated with severe malaria. We measured 25-hydroxyvitamin D [25(OH)D] by immunoassay in a sample of Ugandan children aged 18 months –12 years with severe malaria (cerebral malaria or severe malarial anemia, n = 40) and in healthy community children (n = 20). Ninety-five percent of children with severe malaria (n = 38) and 80% of control children (n = 16) were vitamin D-insufficient [plasma 25(OH)D <30 ng/mL]. Mean plasma 25(OH)D levels were significantly lower in children with severe malaria than in community children (21.2 vs. 25.3 ng/mL, p = 0.03). Logistic regression revealed that for every 1 ng/mL increase in plasma 25(OH)D, the odds of having severe malaria declined by 9% [OR = 0.91 (95% CI: 0.84, 1.0)]. These preliminary results suggest that vitamin D insufficiency may play a role in the development of severe malaria. Further prospective studies in larger cohorts are indicated to confirm the relationship of vitamin D levels to severity of malaria infection and to investigate causality.     

Intellectual Disability Is Associated with Increased Runs of Homozygosity in Simplex Autism

Intellectual disability (ID), often attributed to autosomal-recessive mutations, occurs in 40% of autism spectrum disorders (ASDs). For this reason, we conducted a genome-wide analysis of runs of homozygosity (ROH) in simplex ASD-affected families consisting of a proband diagnosed with ASD and at least one unaffected sibling. In these families, probands with an IQ ≤ 70 show more ROH than their unaffected siblings, whereas probands with an IQ > 70 do not show this excess. Although ASD is far more common in males than in females, the proportion of females increases with decreasing IQ. Our data do support an association between ROH burden and autism diagnosis in girls; however, we are not able to show that this effect is independent of low IQ. We have also discovered several autism candidate genes on the basis of finding (1) a single gene that is within an ROH interval and that is recurrent in autism or (2) a gene that is within an autism ROH block and that harbors a homozygous, rare deleterious variant upon analysis of exome-sequencing data. In summary, our data suggest a distinct genetic architecture for participants with autism and co-occurring intellectual disability and that this architecture could involve a role for recessively inherited loci for this autism subgroup.     

Increased Feeding Speed Is Associated with Higher Subsequent Sympathetic Activity in Dogs

Although the domestication process has altered the feeding behavior of dogs, some breeds still demonstrate a remarkable ability to gorge, and will eat exceptionally large quantities of food whenever it is available. Lesions in the ventromedial hypothalamus increase appetite and lead to obesity, suggesting that the autonomic nervous system plays an important role in feeding. Focusing on the autonomic activities closely involved in food intake, we investigated sympathetic activities before and after feeding in dogs. The subjects were 56 healthy dogs of 21 different breeds (29 males and 27 females). Based on feeding habits, the 56 dogs were divided into three groups: Fast (n = 19), Slow (n = 24) and Leftover (n = 13). The feeding speed and the amount of food per mouthful of the Fast dogs were significantly greater than those of the Slow and the Leftover dogs. The plasma norepinephrine level in dogs of the Fast group was significantly increased after feeding, while those in the Slow and Leftover groups were significantly decreased after feeding, compared with the pre-feeding concentrations. The low frequency/high frequency ratio of heart rate variability is a good indicator of sympathetic activity and was also significantly higher in the Fast group than in the other groups. Delayed feeding using automatic feeding equipment decreased the plasma norepinephrine concentration and low frequency/high frequency ratio observed after feeding in dogs of the Fast group. In conclusion, dogs eating rapidly with less chewing, which indicates increased sympathetic activity during feeding, may benefit from delayed feeding. The slow eating may activate the parasympathetic nervous system after feeding, which could enhance the activity of the digestive system.     

GIMAP5 Deficiency Is Associated with Increased AKT Activity in T Lymphocytes

Long-term survival of T lymphocytes in quiescent state is essential to maintain their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5) causes peripheral T lymphopenia due to spontaneous death of T cells. The underlying mechanism responsible for the disruption of quiescence in Gimap5 deficient T cells remains largely unknown. In this study, we show that loss of functional Gimap5 results in increased basal activation of mammalian target of rapamycin (mTOR), independent of protein phosphatase 2A (PP2A) or AMP-activated protein kinase (AMPK). Our results suggest that the constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway may be one of the consequences of the absence of functional GIMAP5.     

Helminth Colonization Is Associated with Increased Diversity of the Gut Microbiota

Soil-transmitted helminths colonize more than 1.5 billion people worldwide, yet little is known about how they interact with bacterial communities in the gut microbiota. Differences in the gut microbiota between individuals living in developed and developing countries may be partly due to the presence of helminths, since they predominantly infect individuals from developing countries, such as the indigenous communities in Malaysia we examine in this work. We compared the composition and diversity of bacterial communities from the fecal microbiota of 51 people from two villages in Malaysia, of which 36 (70.6%) were infected by helminths. The 16S rRNA V4 region was sequenced at an average of nineteen thousand sequences per samples. Helminth-colonized individuals had greater species richness and number of observed OTUs with enrichment of Paraprevotellaceae, especially with Trichuris infection. We developed a new approach of combining centered log-ratio (clr) transformation for OTU relative abundances with sparse Partial Least Squares Discriminant Analysis (sPLS-DA) to enable more robust predictions of OTU interrelationships. These results suggest that helminths may have an impact on the diversity, bacterial community structure and function of the gut microbiota.     

Rs4074134 Near BDNF Gene Is Associated with Type 2 Diabetes Mellitus in Chinese Han Population Independently of Body Mass Index

Obesity and family history are the most important predictors for type 2 diabetes mellitus(T2DM) in the Chinese Han population. However, it is not known whether the genetic loci related to obesity are associated with the risk of developing T2DM in this population. The present case-control study evaluated the associations between five genetic loci for obesity and the pathogenesis of T2DM. The study included 1117 Chinese Han patients with T2DM, 1629 patients with pre-diabetes (impaired fasting glucose and impaired glucose tolerance, IFG/IGT) and 1113 control subjects residing in Beijing. Five genetic loci including rs2815752 near NEGR1, rs10938397 near GNPDA2, rs4074134 near BDNF, rs17782313 near MC4R and rs1084753 near KCTD15 were genotyped. The results showed an association between rs4074134-BDNF minor allele and T2DM irrespective of age, gender and body mass index (BMI) (OR = 0.87; 95%CI: 0.77–0.99, P = 0.04). This SNP was also associated with pre-diabetes (OR = 0.87; 95%CI: 0.77–0.97, P = 0.01) independently of age, gender and BMI. No associations were found between diabetes or pre-diabetes and any of the other SNP loci studied. Genotype–phenotype association analysis (adjusting for age and gender) showed rs4074134-BDNF to be associated with BMI, waist circumference, fasting and postprandial plasma glucose, fasting serum insulin, and HOMA-IR in subjects without T2DM. However, fasting and postprandial plasma glucose were the only significant factors after adjusting for BMI. These results suggest that the common variation of BDNF (rs4074134) is associated with T2DM independently of obesity in Chinese Han population. This variant also has an effect on plasma glucose concentration, BMI and insulin sensitivity.