-
1.
Impact of NR5A2 and RYR2 3'UTR polymorphisms on the risk of breast cancer in a Chinese Han population.
Wei, Y, Wang, X, Zhang, Z, Zhao, C, Chang, Y, Bian, Z, Zhao, X
Breast cancer research and treatment. 2020;(1):1-8
Abstract
OBJECTIVES The NR5A2 and RYR2 genes are important players in steroid metabolism and play an important role in cancer research. In this research, we want to evaluate the effect of NR5A2 and RYR2 polymorphisms on breast cancer (BC). METHODS Four single nucleotide polymorphisms on NR5A2 and RYR2 were selected to genotype by Agena MassARRAY in 379 BC patients and 407 healthy controls. Using the PLINK software to calculate the Odds ratio (OR) and 95% confidence intervals (CIs) via the logistic regression analysis to evaluate the risk for BC. RESULTS We found that NR5A2 rs2246209 significantly decreased the risk of BC with the AA genotype (OR 0.58, 95%CI 0.34-0.99, p = 0.049), and recessive model (OR 0.59, 95%CI 0.35-0.99, p = 0.046); rs12594 in the RYR2 gene significantly decreased the risk of BC in the GG genotype (OR 0.44, 95%CI 0.22-0.88, p = 0.020), and recessive model (OR 0.43, 95%CI 0.21-0.85, p = 0.016). Further stratification analysis showed that NR5A2 rs2246209 was related to a lower incidence of BC affected by age, lymph nodes metastasis, and tumor stage; RYR2 rs12594 was related to a decreased BC risk restricted by age, estrogen receptor (ER), progesterone receptor (PR), menopausal status, tumor size, and tumor stage. Rs12594 in the RyR2 gene remained significant on the genetic susceptibility of PR-positive BC after Bonferroni correction (p < 0.0125). CONCLUSIONS This study provides an evidence that NR5A2 rs2246209 and RYR2 rs12594 decreased the risk of breast cancer.
-
2.
The relationships between macronutrient and micronutrient intakes and type 2 diabetes mellitus in South Asians: A review.
Shah, M, Garg, A
Journal of diabetes and its complications. 2019;(7):500-507
Abstract
BACKGROUND South Asians (SA) have increased prevalence of type 2 diabetes mellitus (T2DM). The role of nutrient intakes in T2DM in SA is not well understood, however. OBJECTIVE The paper reviewed the relationship between macronutrient and micronutrients intakes and T2DM in SA. METHODS The MEDLINE database was searched for relevant papers on this topic in SA. RESULTS There was some evidence that dietary fiber and linoleic acid intake may reduce but carbohydrates may increase the risk of T2DM. Some studies found higher energy from protein and fat in subjects with T2DM versus controls. Other studies, however, found lower carbohydrate intake among those with T2DM or no relationship between diet composition and T2DM. Several vitamins and minerals were also inversely related to T2DM. CONCLUSIONS The data were limited to a few epidemiological studies. Most studies did not distinguish between undiagnosed and known T2DM. Subjects with known T2DM are more likely to have changed their diet. Prospective cohort or randomized controlled studies examining the role of diet composition, using precise image-assisted dietary assessment method and blood biomarkers, in the development of T2DM among migrant and native SA are needed. Lastly, a more complete nutrient database for foods consumed by SA is needed.
-
3.
FTO gene polymorphisms and obesity risk in Chinese population: a meta-analysis.
Zhao, NN, Dong, GP, Wu, W, Wang, JL, Ullah, R, Fu, JF
World journal of pediatrics : WJP. 2019;(4):382-389
Abstract
BACKGROUND There is tremendous increase in obesity worldwide. Many factors including diet, life style, genetic, and epigenetic changes contribute to obesity. The fat mass and obesity-associated (FTO) gene polymorphisms are strongly associated with obesity. It has been reported that FTO single-nucleotide polymorphisms (SNPs) are associated with obesity in European populations; however, it was controversial in Chinese population. The present meta-analysis study was designed to investigate the association between FTO polymorphisms and obesity risk in Chinese population. METHODS The investigators searched studies using the following databases: PubMed, web of science, and Cochrane Central Register of Controlled Trials. A random-effects model was used to calculate the pooled odds ratios (ORs). The heterogeneity among the studies was measured by I2 value. Subgroup analysis was used to find out the potential factors influencing the heterogeneity. RESULTS A total of 18 articles including 26 studies were included in the present meta-analysis. Overall, the FTO SNPs were significantly associated with obesity in Chinese population (OR 1.30; 95% CI 1.19-1.42; P < 0.001) under per-allele comparison. The subgroup analysis also showed strong association between four FTO SNPs (rs9939609, rs6499640, rs8050136, and rs1558902) and obesity risk. Furthermore, subgroup analysis stratified by children/adolescent and adult groups showed same trend. CONCLUSION The present meta-analysis indicated that FTO SNPs are associated with obesity risk in both children/adolescents and adults in Chinese population.
-
4.
A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature.
Li, S, Yang, Y, Huang, L, Kong, M, Yang, Z
Molecular medicine reports. 2019;(5):4364-4376
-
-
Free full text
-
Abstract
Familial renal glucosuria (FRG) is a rare condition that involves isolated glucosuria despite normal blood glucose levels. Mutations in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium‑glucose cotransporter 2 (SGLT2), have been reported to be responsible for the disease. Genetic testing of the SLC5A2 gene was conducted in a Chinese family with FRG. A number of online tools were used to predict the potential effect of the identified mutations on SGLT2 function. Additionally, the SLC5A2 mutations previously reported in PubMed were summarized. A novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene in a Chinese child with FRG was identified. In total, 86 mutations of the SLC5A2 gene have been reported to be associated with FRG. The novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene may be responsible for the onset of FRG. The present study provides a starting point for further investigation of the molecular pathogenesis of the SLC5A2 gene mutation in patients with FRG.
-
5.
A novel PHKA2 mutation in a Chinese child with glycogen storage disease type IXa: a case report and literature review.
Fu, J, Wang, T, Xiao, X
BMC medical genetics. 2019;(1):56
Abstract
BACKGROUND PHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa). Elevated liver transaminase levels and liver enlargement are the most frequent phenotypes of GSD IXa. However, whether the phenotypes are applicable to Chinese patients remains unclear. CASE REPORT A boy aged 2 years and 8 months with a history of episodic fatigue and weakness since he was 2 years old was referred to our endocrinology clinic. Apart from symptomatic ketotic hypoglycemic episodes (palpitation, hand shaking, sweating, etc.), no abnormalities of liver transaminase levels or liver size were found. To identify the aetiology of his clinically diagnosed hypoglycaemia, the proband and his parents were screened for PHKA2 gene mutations by next-generation sequencing. A heterozygous mutation (c.2972C > G, p.G991A) in PHKA2 was found in the proband and his mother. Twenty-one Chinese cases with GSD IXa have been reported in the literature to date, and elevated liver transaminase levels (95%) and liver enlargement (91%) are the most frequent phenotypes of GSD IXa in Chinese patients. Hypoglycaemia may be one of the early onset symptoms in infants with GSD IXa. CONCLUSIONS This study enriches our knowledge of the PHKA2 gene mutation spectrum and provides further information about the phenotypic characteristics of Chinese GSD IXa patients.
-
6.
Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients.
Momosaki, K, Kido, J, Yoshida, S, Sugawara, K, Miyamoto, T, Inoue, T, Okumiya, T, Matsumoto, S, Endo, F, Hirose, S, et al
Journal of human genetics. 2019;(8):741-755
Abstract
A newborn screening program for Pompe disease using dried blood spots (DBSs) was initiated in Japan. Here, we summarized this screening program and described the results of the GAA gene analysis. From April 2013 to November 2016, 103,204 newborns were screened; 71 had low acid alpha-glucosidase (AαGlu) activity. GAA sequencing showed that 32 (45.1%) and 37 (52.1%) of these newborns were homozygous and heterozygous for pseudodeficiency alleles c.[1726G>A; 2965G>A], respectively. Moreover, 24 of 32 newborns with homozygous c.[1726G>A; 2965G>A] alleles had no mutations, and the other eight had one mutation each. Thirty-five of 37 newborns with heterozygous c.[1726G>A; 2965G>A] alleles had one mutation, and the other two had two mutations each. Only one newborn who had two mutations did not harbor c.[1726G>A; 2965G>A] alleles. Thus, it was difficult to distinguish newborns with c.[1726G>A; 2965G>A] alleles from newborns with pre-symptomatic Pompe disease using AαGlu assays in DBSs or fibroblasts; GAA gene sequencing was necessary. Seventy-one newborns had 50 variants, including 21 mutations or predictably pathogenic variants, and 29 polymorphisms or predictably non-pathogenic variants. Four of 21 mutations or predictably pathogenic variants and four of 29 polymorphisms or predictably non-pathogenic variants were novel. No infantile-onset Pompe disease was detected, and three newborns were diagnosed with potential late-onset Pompe disease. In the literature, 156 variants have been reported for 296 patients from 277 families in 41 articles from Japan, Korea, Taiwan, and China. Our results provide insights into GAA gene mutation profiles and the relationship between GAA and Pompe disease in Asian populations.
-
7.
Clinical management of type 2 diabetes in south Asia.
Misra, A, Sattar, N, Tandon, N, Shrivastava, U, Vikram, NK, Khunti, K, Hills, AP
The lancet. Diabetes & endocrinology. 2018;(12):979-991
Abstract
Compared with other ethnic groups, south Asian people with type 2 diabetes tend to develop the disease at a younger age and manifest with higher glycaemia, dyslipidaemia, nephropathy, and cardiovascular diseases. Additionally, specific issues that can affect treatment of type 2 diabetes in south Asia include poor awareness of the disease, delay in diagnosis, inadequate treatment, the use of ineffective and often harmful alternative medicines, and frequent non-compliance with lifestyle recommendations and drug treatment. Disease development at younger ages, delayed diagnosis, and inadequate management result in early development of severe complications and premature mortality. In this Series paper, we describe the challenges associated with the increasing burden of type 2 diabetes in south Asia and discuss ways to improve clinical care of people with the disorder in the region (defined to include Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka). Treatment of diabetes in south Asia needs to be individualised on the basis of diverse and heterogeneous lifestyle, phenotype, environmental, social, cultural, and economic factors. Aggressive management of risk factors from diagnosis is necessary to reduce the risk of microvascular and macrovascular complications, focusing on provision of basic treatments (eg, metformin, low-cost statins, and blood pressure-lowering drugs) and other interventions such as smoking cessation. Strengthening of the primary care model of care, better referral linkages, and implementation of rehabilitation services to care for patients with chronic complications will be important. Finally, improvement of physicians' skills, provision of relevant training to non-physician health-care workers, and the development and regular updating of national clinical management guidelines will also be crucial to improve diabetes care in the region.
-
8.
Long-term follow-up in a Chinese child with congenital lipoid adrenal hyperplasia due to a StAR gene mutation.
Zhao, X, Su, Z, Liu, X, Song, J, Gan, Y, Wen, P, Li, S, Wang, L, Pan, L
BMC endocrine disorders. 2018;(1):78
Abstract
BACKGROUND Congenital lipoid adrenal hyperplasia (CLAH) is an extremely rare and the most severe form of congenital adrenal hyperplasia. Typical features include disorder of sex development, early-onset adrenal crisis and enlarged adrenal glands with fatty accumulation. CASE PRESENTATION We report a case of CLAH caused by mutations in the steroidogenic acute regulatory protein (StAR) gene. The patient had typical early-onset adrenal crisis at 2 months of age. She had normal-appearing female genitalia and a karyotype of 46, XY. The serum cortisol and adrenal steroids levels were always nearly undetectable, but the adrenocorticotropic hormone levels were extremely high. Genetic analysis revealed compound heterozygous mutations at c. 229C > T (p.Q77X) in exon 3 and c. 722C > T (p.Q258X) in exon 7 of the StAR gene. The former mutation was previously detected in only two other Chinese CLAH patients. Both mutations cause truncation of the StAR protein. The case reported here appears to be a classic example of CLAH with very small adrenal glands and is the second reported CLAH case with small adrenal glands thus far. In a 15-year follow-up, the patient's height was approximately average for females before age 4 and fell to - 1 SDS at 10 years of age. Her bone age was similar to her chronological age from age 4 to age 15 years. CONCLUSIONS In conclusion, this is a classic case of CLAH with exceptionally small adrenal glands. Q77X mutation seems to be more common in Chinese CLAH patients. Additionally, this is the first report of the growth pattern associated with CLAH after a 15-year follow-up.
-
9.
Body fat, metabolic syndrome and hyperglycemia in South Asians.
Misra, A, Soares, MJ, Mohan, V, Anoop, S, Abhishek, V, Vaidya, R, Pradeepa, R
Journal of diabetes and its complications. 2018;(11):1068-1075
Abstract
The prevalence of overweight and obesity is escalating in South Asian countries. South Asians display higher total and abdominal obesity at a lower BMI when compared to Whites. Consequently, metabolic dysfunction leading to metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) will account for a majority of the health burden of these countries. In this review, we discuss those factors that contribute to MetS and T2DM in South Asians when compared to whites, focusing on adiposity. Abdominal obesity is the single-most important risk factor for MetS and its predisposition to T2DM. Excessive ectopic fat deposition in the liver (non-alcoholic fatty liver disease) has been linked to insulin resistance in Asian Indians, while the effects of ectopic fat accumulation in pancreas and skeletal muscle need more investigation. South Asians also have lower skeletal muscle mass than Whites, and this may contribute to their higher risk T2DM. Lifestyle factors contributing to MetS and T2DM in South Asians include inadequate physical activity and high intakes of refined carbohydrates and saturated fats. These are reflective of the recent but rapid economic transition and urbanization of the South Asian region. There is need to further the research into genetic determinants of dysmetabolism as well as gene x environment interactions. Collectively, MetS and T2DM have multi-factorial antecedents in South Asians and efforts to combat it through low-cost and socio-culturally appropriate lifestyle interventions need to be supported.
-
10.
Regional evidence and international recommendations to guide lipid management in Asian patients with type 2 diabetes with special reference to renal dysfunction.
Lau, TW, Tan, KEK, Choo, JCJ, Ng, TG, Tavintharan, S, Chan, JCN
Journal of diabetes. 2018;(3):200-212
Abstract
The anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular-renal complications, will place a significant burden on patients, caregivers, and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps, especially in Asian patients with young-onset diabetes and chronic kidney disease (CKD). Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity. These recommendations replaced the previous strategy of using low-density lipoprotein cholesterol targets to guide initiation and intensification of lipid lowering, albeit still widely practiced in Asia. The latest guidelines also highlight the high risk of atherosclerosis and cardiovascular disease (ASCVD) for people with diabetes, who should be protected with statins, except for young patients without other risk factors, who will need yearly monitoring of blood lipid levels. Given the propensity of Asian patients with diabetes to develop CKD and the amplifying effect of CKD on ASCVD, the use of statins in Asian patients is particularly important. Due to interethnic differences in drug metabolism, rosuvastatin, which is largely cleared by the kidney, should be prescribed in low dosages (5-10 mg daily) in Asian populations. Conversely, epidemiological and experimental data confirm pleotropic and organ-protective effects of atorvastatin, with proven safety in Asian populations within a daily dose range of 10-40 mg. Thus, there is a need for Asian countries to review and align their lipid-lowering treatment guidelines to reduce the substantial burden of diabetes in the Asian region.