Pancreatic A cell function was studied in 119 cases of NIDDM with 37 normal subjects as controls. In NIDDM group, fasting plasma glucagon leveh averaged 192.9 ? 129.6 pg /ml, whereas in normals being 132.8?65.0 pg / ml. Plasma glucagon levels were markedly elevated in patients with NIDDM irrespective of insulin administration, suggesting decreased pancreatic A cell sensitivity to glucose.In 7 male normal subjects, following intravenous injection of insulin (0.1 U / kg) an average increment of 114 pg / ml of plasma glucagon level with a peak at 30-60 min was noted. In 3 of 6 male diabetic subjects a paradoxical reduced plasma glucagon response to insulin-induced hypoglycemia was demonstrated, suggesting primary abnormality of pancreatic A cell function in NIDDM patients, with a possible defect in glucose counter-regulation.

Objective To study the expressions of matrix metalloproteinase (MMP) gene family in papillary thyroid carcinoma (PTC) and its relationship to the pathogenesis of PTC. Methods The thyroid tissues of patients were collected in surgical operation, including 8 cases with papillary thyroid carcinoma, 7 cases with Hashimoto′s thyroiditis, 8 cases with adenoma and 8 normal tissues. The total RNA of these samples were extracted and purified by the method of acidic phenol. The gene expressions of MMP-2, MMP-9, MMP-14, MMP-25 and MMP-26 were assayed by RT-PCR and 1% agarose gel electrophoresis. The fluorescent degree of electrophoretic bands was detected by automatic gel scanner and analyzed statistically in order to compare the levels of gene expressions among 4 groups. Results The positive rates and the levels of MMP-2, MMP-9 and MMP-14 gene expressions in PTC group were significantly higher than those in other 3 groups (all P

Objective: To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis. Methods: A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method. Results: A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m². Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (β=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (β=0.04, P=0.007) and closely related to cg15053022 (F=237.66, P=0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (β=-1.97, P<0.001). Conclusion This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.

Objective:To explore the genetic and environmental effects on alcohol intake.Methods:Data on 9 231 pairs of adult twins of the same sex was collected from the Chinese National Twin Registry (CNTR), between 2015 and 2018 and used in this study. Structural equation model was used to estimate the effects of genetic and environmental factors on alcohol intake.Results:A total of 9 231 pairs of twins were included in the analysis, of which 6 085 pairs were monozygotic (MZ). The average age of MZ was (36.91±13.07) years old, and males accounted for 56.80 %. The average age of dizygotic twins (DZ) was (35.22±12.48) years old, and males accounted for 55.91 %. There were 350 pairs of alcohol-drinking twins were with high-risk, accounting for 1.90 % and another 367 pairs (1.99 %) were with medium-risk. Alcohol-drinkers with medium-risk were affected by additive genetics, common and unique environmental factors, seen among the twins. The overall heritability appeared as 24.3 % (95 %CI: 0 to 56.8 %). Furthermore, 50.7 % of the variation (95 %CI: 20.4 %-79.0 %) could be explained by the common environmental factors and 24.9 % (95 %CI: 18.3 %-36.5 %) by unique environmental factors. High-risk related drinking behavior was affected by both common and unique environmental factors. The common environmental component appeared as 75.6 % (95 %CI: 69.6 %-80.8 %) and unique environmental component as 24.4 % (95 %CI: 19.2 %-30.4 %), respectively. Gender difference was seen in the heritability of those with medium or high-risk drinking behaviors. The heritability of men was 30.8 % (95 %CI: 9.8 %-53.5 %), while in women it was mainly affected by the environment. Conclusion:Both alcohol drinkers with medium and high-risk drinking behaviors were mainly affected by the environment factors and gender. With the increase of drinking volume, the effect of environment on drinking behaviors became more obvious.

Objective:To quantitate the association between birth weight and phenotypes of physical indicators in adulthood, i.e. BMI and waist circumference (WC) and to what degree genetic or environmental factors affect birth weight-obesity association.Methods:A total of 6 623 gender matched twin pairs aged 25 to 79 years were recruited through the Chinese National Twin Registry. The twins reported their own birth weight, current height and weight, and WC using a self-administered questionnaire. BMI was calculated according to the self-reports of body height and weight. Within twin-pair design was used to quantitate the association between birth weight and phenotypes related to obesity while bivariate structural equation models were used to decompose the phenotype correlation.Results:After adjusted for multiple factors, twin-pair analyses within monozygotic (MZ) showed that, on average, a 1.0 kg increase in birth weight corresponded to an increase of 0.33 kg/m 2 in BMI and 0.95 cm in WC in adulthood ( P<0.001). Bivariate structural equation models showed significant positive unique environmental correlation between birth weight and the two obesity-related phenotypes. Conclusion:The study supported the role of twin-specific supply line factors on relationship between birth weight and physical indicators in adulthood.

Objective:To analyze the heritability of coronary heart disease (CHD) among the Chinese twin adults.Methods:A total of 20 477 same-sex twin pairs aged 25 years and older from the Chinese National Twin Registry were interviewed. Structure equation model was used to estimate the heritability of CHD.Results:After adjusting for age and gender, the overall heritability of CHD was 0.75(0.68-0.81). Stratified analyses showed that genetic factors play a more important role in CHD incidence in ≥40 years or female twins. While the development of CHD was mainly influenced by environmental factors in 25-39 years or male twins.Conclusion:CHD is influenced by both genetic and environmental factors and the heritability is high.

Objective:To describe the differences in body mass index (BMI) distribution in adult twins registered in Chinese National Twin Registry (CNTR), and provide evidence for the risk factor analysis and prevention and control of overweight or obesity.Methods:A total of 32 725 twin pairs aged 18 years and above who completed the questionnaire survey during 2010-2018 and had complete registered information in CNTR and normal body weight and length were included in the analysis on the population and region specific distributions of BMI of twin pairs and the difference in BMI in twin pairs.Results:The twin pairs included in the analysis were aged (34.6±12.4) years, the twin pairs of same gender accounted for 79.7%. The average BMI was 22.5 kg/m 2. The overall prevalence of obesity and overweight was 4.9% and 23.7%, respectively. Participants who were men, 50-59 years old, married, had lower education level, and lived in northern China had higher overweight rate and obesity rate ( P<0.001). The difference in overweight or obesity prevalence between monozygotic (MZ) twin pars and dizygotic (DZ) twin pairs was not significant, but firstborn twin pairs had slightly higher rates of overweight and obesity than later-born twin pairs ( P<0.05). The analysis in same gender-twin pairs indicated that the difference in BMI was associated with age (trend test: P<0.001), and the difference was more obvious in DZ twin pair in MZ pair and this difference increased with age. The concordant rate of BMI was higher in MZ twin pairs than DZ twin pairs ( P<0.05). Conclusion:The distribution of BMI of twin pairs varied with population and region and BMI varied with age due to its genetic nature.

Objective:To explore the modification effect of physical activity on the genetic effects of type 2 diabetes mellitus (T2DM).Methods:The univariate moderation model was fitted to calculate the modifying effect of physical activity on the genetic effects of T2DM based on the data of 12 107 pairs of same gender twins aged 30 years and older enrolled by the Chinese National Twin Registry in 11 provinces/cities in China.Results:After adjusting for age and gender, the heritability of T2DM was 0.56 (0.31-0.84). Qualified physical activity could attenuate the genetic effects of T2DM. The heritability of T2DM in twin pairs with qualified physical activity was 0.46 (0.06-0.88), which was lower than that in twin pairs without qualified physical activity during the same model [0.68(0.36-0.94)].Conclusion:T2DM is a moderate genetic disease, physical activity can modify the genetic effects of T2DM.

Objective:To explore the gene-body mass index (BMI) interaction on coronary heart disease (CHD) in the Chinese adult twins.Methods:A total of 20 340 same-sex twin pairs registered in the Chinese National Twin Registry (CNTR) were enrolled in this study. Classical twin structure equation model was used to estimate the gene-BMI interaction on CHD.Results:After adjusting for age, we found that genetic variance of CHD differed as the function of BMI in male twins, which indicated the presence of a gene-BMI interaction on CHD ( P=0.008).The genetic moderating effect ( βa) was -0.14 (95% CI: -0.22--0.04), indicating that for each logarithmic transformation value of BMI increase, genetic path parameters would decrease by 0.14, which would result in the decrease of genetic variance of CHD. And the heritability of CHD was 0.77 (95% CI: 0.65-0.86) among the male twins with lower BMI (<24.0 kg/m 2), but 0.56 (95% CI: 0.33-0.74) among the male twins with high BMI (≥24.0 kg/m 2). However, there was no evidence suggesting that BMI could moderate genetic variants of CHD in female. Conclusion:We found a significant gene-BMI interaction on CHD in the Chinese male adult twins in China, and the heritability of CHD was higher among the twins whose BMI was <24.0 kg/m 2.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.