An analysis of targeted single nucleotide polymorphisms for the risk prediction of gestational diabetes mellitus in a cohort of Malaysian patients (original) (raw)
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Sains Malaysiana
Gestational Diabetes Mellitus (GDM) is associated with pregnancy complications, however its mechanism has not been fully understood. The aim of this study was to investigate the single nucleotide polymorphism (SNP) for identifying candidate genes involve in risk factors and complications of GDM. A total of 174 pregnant women with GDM and 114 healthy pregnant women were genotyped with 384 SNPs from 236 genes. The SNPs identified were rs10946398 (CDKAL1) in GDM risk factors; rs328 (LPL) and rs1042778 (OXTR) in complications of caesarean section; rs5404 (SLC2A2), rs5400 (SLC2A2) and rs13306465 (IRS1) for neonatal intensive care admission. Whereby SNPs rs12255372, rs7901695 and rs7903146 from TCF7L2 gene had six times higher risk (OR, 6.40-6.53) for T2DM at postpartum. In conclusion, although the above SNPs were identified with GDM risk factors and complications among pregnant Malaysian women with GDM, a larger study is needed to ascertain this candidate genes actual association. ABSTRA...
Endocrine journal, 2017
Gestational diabetes (GDM) and type 2 diabetes (T2DM) share part of pathomechanism and several T2DM susceptibility genes are demonstrated to be associated with GDM. No information on the genetics of GDM, however, was available in Japanese women. In this study, T2DM risk variants (45 single nucleotide polymorphisms [SNPs] from 36 genes) identified in previous studies were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a cohort of 171 Japanese women with GDM and 128 normal glucose tolerance (NGT) diagnosed by the new International Association of Diabetes in Pregnancy Study Group criteria. Of 45 SNPs, three genetic variants were nominally associated with the development of GDM: rs266729 (p = 0.013, odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.10-2.23) in ADIPOQ, rs10811661 (p = 0.035, OR: 1.46, 95% CI: 1.03-2.08) in CDKN2A/2B, and rs9505118 (p = 0.046, OR: 1.41, 95% CI: 1.01-1.97) in SSR1-RREB1. There was a significant differen...
Diabetologia, 2018
Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse. We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate. For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants...
Genetic variants and the risk of gestational diabetes mellitus: a systematic review
Human Reproduction Update, 2013
† Introduction † Methods † Results † Discussion background: Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies. methods: Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity. results: Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (230G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P , 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P ¼ 0.002) per T allele of rs12255372. conclusions: In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Genetic risk factors associated with gestational diabetes in a multi-ethnic population
PLoS ONE, 2021
Aims Genome-wide association studies have shown an increased risk of type-2-diabetes (T2DM) in patients who carry single nucleotide polymorphisms in several genes. We investigated whether the same gene loci confer a risk for gestational diabetes mellitus (GDM) in women from Hawaii, and in particular, Pacific Islander and Filipino populations. Methods Blood was collected from 291 women with GDM and 734 matched non-diabetic controls (Pacific Islanders: 71 GDM, 197 non-diabetic controls; Filipinos: 162 GDM, 395 controls; Japanese: 58 GDM, 142 controls). Maternal DNA was used to genotype and show allele frequencies of 25 different SNPs mapped to 18 different loci. Results After adjusting for age, BMI, parity and gravidity by multivariable logistic regression, several SNPs showed significant associations with GDM and were ethnicity specific. In particular, SNPs rs1113132 (EXT2), rs1111875 (HHEX), rs2237892 (KCNQ1), rs2237895 (KCNQ1), rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed si...
Genetic Risk Analysis of Gestational Diabetes Mellitus in a Turkish Population
Research in Molecular Medicine, 2021
Background: Gestational diabetes mellitus (GDM) is a type of clinical diabetes characterized by insulin resistance and impaired insulin secretion because of environmental and genetic factors. The high risk of developing type 2 diabetes (T2D) in women with GDM and the high risk of developing GDM in women with a family history of T2D suggests that both diseases may have the same genetic basis. Therefore, genes and risk variants associated with the genetic architecture of T2D are being investigated for their effects on the development of GDM. In this study, we aim to investigate ABCC8, TCF7L2, Adiponectin, IRS1, and PPARG genes, which are known as T2D risk genes, to understand the genetic basis of GDM in a Turkish population. Materials and Methods: In our study, 74 pregnant women diagnosed with GDM according to the American Diabetes Association criteria and 49 healthy pregnant women were included. DNA isolations were made from peripheral blood cells collected from pregnant women and regions of targeted genes were scanned by the Polimerase Chain Reaction-Restriction fragment length polymorphism (PCR-RFLP) technique. The homeostatic model assessment for insulin resistance (HOMA-IR), which is an indicator of insulin resistance, was calculated for each individual in the biochemical examinations. The associations of genotypes detected in the target gene regions with the disease and their effects on the biochemical phenotypes were analyzed by establishing the dominant, recessive, and additive models along with calculating odd ratios. The P<0.05 was considered statistically significant in all analyses. Results: A statistically significant association was found between R1273R substitution in the ABCC8 gene and GDM under dominant and additive models. No statistically significant correlation was found between the A1369S and e16/-3t→c variants in the ABCC8 gene and the screened variants in other genes and GDM. When the genotype-phenotype association data was evaluated, no association was detected between all the scanned variants and fasting blood sugar while a weak correlation was found between e16/-3t→c in the ABCC8 gene and fasting insulin (P=0.075) and HOMA-IR (P=0.067). Conclusion: ABCC8 (R1273R and e16/-3t→c) gene variants may be a risk factor for the development of GDM in the Turkish population.
Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus
Diabetes Research and Clinical Practice, 2012
Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74) respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p=0.00016 after adjustment for age and ethnicity). Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.
The Genetic Risk of Gestational Diabetes in South Asian women
ABSTRACTSouth Asian women are at increased risk of developing gestational diabetes (GDM). Few studies have investigated the genetic contributions to GDM risk. We investigated the association of a type 2 diabetes (T2D) polygenic risk score (PRS), on its own, and with GDM risk factors, on GDM-related traits using data from two birth cohorts in which South Asian women were enrolled during pregnancy. 837 and 4,372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-gram glucose tolerance test. PRSs were derived using GWAS results from an independent multi-ethnic study (∼18% South Asians). Associations with fasting plasma glucose (FPG); 2h post-load glucose (2hG); area under the curve glucose; and GDM were tested using linear and logistic regressions. The population attributable fraction (PAF) of the PRS was calculated. Every 1 SD increase in the PRS was associated with a 0.085 mmol/L increase in FPG ([95%CI=0.07-0...