Investigation of the Association between 45 Tag SNPs and Type 2 Diabetes Mellitus in Han Chinese Adults: A Prospective Cohort Study.

INTRODUCTION: The objective of this study was to examine the association between type 2 diabetes mellitus (T2DM) and genes identified in previous genome-wide association studies (GWASs) in rural Han Chinese adults. METHODS: This prospective study included 1,832 adults aged ≥18 years in Deqing without diabetes at baseline. The subjects were followed up for 8.7 years on average. We selected 45 susceptible tag single-nucleotide polymorphisms (SNPs) for T2DM that have been identified in GWASs and genotyped. A Cox model was constructed to calculate the adjusted hazard ratios (aHRs) for the association between SNPs and incident T2DM. RESULTS: The incidence rate of T2DM was 12.0 per 1,000 person-years. After adjustment for covariates and a Bonferroni correction, rs17584499 of protein tyrosine phosphatase, receptor-type D (PTPRD), rs11257655 and rs10906115 of cell division cycle 123 gene (CDC123), and rs12970134 of melanocortin-4 receptor (MC4R) were significantly associated with incident T2DM. The aHRs for incident T2DM were 1.75 (95% confidence interval [CI]: 1.28-2.40) and 1.61 (95% CI: 1.27-2.04) in association with an increasing number of T alleles in rs17584499 and rs11257655 under an additive genetic model, and the aHR was 1.72 (95% CI: 1.33-2.22) with an increasing number of A alleles in rs10906115. The aHRs under the dominant model were 1.82 (95% CI: 1.25-2.66) for TT + CT versus CC of rs17584499 and 2.04 (95% CI: 1.47-2.86) for AA + AG versus GG of rs10966115. The aHRs under the recessive model were 2.99 (95% CI: 1.30-6.89) for TT versus CT + CC of rs17584499, 1.92 (95% CI: 1.39-2.70) for TT versus CT + CC of rs11257655, and 2.54 (95% CI:1.22-5.29) for AA versus AG + GG of rs12970134. In addition, an increased incidence of T2DM was significantly associated with the TA haplotype of rs11257655 and rs10906115 (aHR = 1.81, 95% CI: 1.12-2.92), while a decreased incidence was associated with the CG haplotype (aHR = 0.49, 95% CI: 0.35-0.68) and the CT haplotype of rs1111875 and rs5015480 (aHR = 0.61, 95% CI: 0.37-0.98). CONCLUSION: Variants of the PTPRD, CDC123, and MC4R genes were associated with the T2DM incidence in a rural Han Chinese population.

Modification effects of T2DM-susceptible SNPs on the reduction of blood glucose in response to lifestyle interventions.

In recent years, it has been demonstrated that some susceptible gene loci of type 2 diabetes mellitus (T2DM) are not only associated with the susceptibility risk of T2DM, but also the modifying effects of lifestyle interventions. To further explore the modifying effects of the single nucleotide polymorphism (SNP) on the onset of T2DM and the reduction of blood glucose in response to lifestyle interventions among the high-risk population, we performed a lifestyle intervention study in two Deqing rural communities during the period from June to December in 2017. The intensive lifestyle interventions were conducted among the study subjects of the intervention group while those in the control group only received conventional and general health education. All participants were genotyped by the MassARRY system. This study showed that for SNP rs9502570, fasting blood glucose showed a significantly greater reduction for individuals with CC + CT genotype than those with TT genotype (P=0.031). In the intervention group, the glycated hemoglobin A1C (HbA1C) decreased by 0.03% for those with CC+CT genotype, while HbA1C increased by 0.27% for those with TT genotype (P=0.012). The difference in the reduction of fasting blood glucose and HbA1c between the intervention and control groups was also statistically significant between individuals with TT and those with CC+CT genotype. For SNP rs10811661, the reduction of fasting blood glucose was significantly higher in people with TT genotype than those with CC + CT genotype (0.44 mmol/L vs 0.12 mmol/L, P=0.021). The difference in reduction of fasting blood glucose between the intervention group and control group was also statistically significant between TT and CC+CT genotype (P<0.001). In summary, the SNP genotypes of both rs9502570 and rs10811661 could modify the effects of lifestyle interventions on reducing fasting blood glucose and HbA1C among the high risk rural population for T2DM. The present study has provided supporting evidence for future development of individualized intervention measures for high-risk population of T2DM.

[Prevalence of occult hepatitis B virus infection and its phylogenetic features among mother-teenager pairs].

OBJECTIVE: Prevalence of occult hepatitis B virus (HBV) infection (OBI) was investigated in a paired mother-teenager population and HBV S gene variation including overt and occult HBV, was determined. METHODS: A follow-up study based on an initial survey of 135 mother-teenager pairs was carried out through collection of questionnaires and blood samples HBsAg were detected by ELISA method, viral load by PCR amplification and HBV S gene by phylogenetic analysis. RESULTS: 102 pairs of subjects were followed-up. Blood samples from 94 mothers and 101 children were collected. OBI prevalence in mothers was 10.0% (6/60), significantly higher than 2.0% (2/101) in teenagers. Medians of viral load were 399.9 IU/ml and 247.6 IU/ml in overt and occult HBV strains, but without significant difference. 1 occult HBV strain belonged to genotype B with serotype adw while the other 7 were genotype C with serotype adr. 15 of the overt HBV strains belonged to genotype B with serotype adw and the other 8 were genotype C with serotype adr. Proportions of genotype-C strains were significantly higher in occult HBV strains than in overt HBV strains. CONCLUSION: OBI was seen in teenage-mother population.

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

[Study on the prevalence and genotype of hepatitis E virus among commercial swine population in Eastern and Southern China].

OBJECTIVE: To determine the prevalence and genotype of hepatitis E virus (HEV) among commercial swine population in Eastern and Southern China. METHODS: Six hundred specimens of swine bile collected from 5 slaughterhouses in Eastern and Southern China from 2007 to 2009 were tested for HEV RNA using nested RT-PCR. PCR products were sequenced for phylogenetic analysis. RESULTS: Forty-seven out of the 600 samples (7.83%) were positive for HEV RNA. Based on the 150 nt fragment within HEV ORF2, data from phylogenetic analysis revealed that all the 47 HEV isolates were identified to be genotype IV, sharing 75.0% - 83.4%, 75.0% - 84.6%, 71.9% - 80.7% and 88.1% - 91.5% nucleotide identities with prototype I, II, III and IV HEV strains respectively while majority of the isolates clustered within their respective isolation sites. CONCLUSION: HEV was widespread in commercial swine population in Eastern and Southern China that raised a serious concern about the safety regarding the consumption of pork products.