Genetic risk factors associated with gestational diabetes in a multi-ethnic population

Abstract

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 significant associations with GDM in Filipinos. For Japanese, SNPs rs4402960 (IGFBP2) and rs2237892 (KCNQ1) were significantly associated with GDM. For Pacific Islanders, SNPs rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM. Individually, none of the SNPs showed a consistent association with GDM across all three investigated ethnicities. Conclusion Several SNPs associated with T2DM are found to confer increased risk for GDM in a multiethnic cohort in Hawaii.

Genetic variants for prediction of gestational diabetes mellitus and modulation of susceptibility by a nutritional intervention based on a Mediterranean diet

“…GRB10 (rs933360) node has strong interaction with the IRS1 node, an insulin receptor substrate 1 that may mediate the control of various cellular processes by insulin. It is associated with diabetes in some studies ( 32 – 34 ), and with both diabetes and GDM in other ( 35 , 36 ). We have found an association with GDM in the Hispanic ethnic stratum.…”

“…Most of the nodes in Figure 2 have the name of a locus/gene that are well referenced in the literature because several SNPs with a significant association with diabetes and GDM are located nearby. Specifically, the nodes located in the central core of the graph, MNTR1B (rs1387153, rs10830962, rs10830963), IGF2BP2 (rs4402960, rs7651090), KCNJ11 (rs5215), GCKR (rs780094), CDKAL1 (rs9368222), IRS1 (rs2943634), ADRA2A (rs10885122), CRY2(rs11605924), DKGB (rs2191349), G6PC2 (rs563694), GLIS3 (rs7041847, rs7034200, rs10814916), GIPR (rs2302593), WFS1 (rs4458523), ZBED3 (rs7708285), PROX1 (rs340874), FOXA2 (rs6048205), PDX1 (rs2293941), PCSK1 (rs6235), have been referred in various GWAS as associated to diabetes ( 6 , 19 – 25 ), GDM ( 26 – 34 ) or both ( 35 , 36 ).…”

Association of solute carrier family 30 A8 zinc transporter gene variations with gestational diabetes mellitus risk in a Chinese population

“…Similarly, previous research has demonstrated that the T allele of rs13266634 protects against the risk of GDM in the Swedish population ( 8 ), which was consistent with our findings. Moreover, in populations of Filipinos, Swedes, Koreans, and Chinese individuals, there was evidence of an association between the C allele of SLC30A8 rs13266634 and a higher risk of GDM ( 8 , 13 , 14 , 18 ). However, other studies have not found any association between rs13266634 and the risk of GDM in populations of Danes and Europeans ( 15 – 17 ).…”

Genetic risk score to improve prediction and treatment in gestational diabetes mellitus

“…Another study suggested that SLC30A8 rs13266634/T is a protective variant against the development of GDM among European women (46). SLC30A8 rs13266634/T also showed significant associations with GDM among Filipinos (52). Furthermore, SLC30A8 rs3802177 was also significantly associated with the risk of GDM (25).…”