Association of KCNJ11 with impaired glucose regulation in essential hypertension

Abstract

ABSTRACT. KCNJ11 is one of the candidate genes for type 2 diabetes, confirmed by genome wide association study, but there are little data on the relationship between KCNJ11 and impaired glucose regulation in essential hypertension patients. To identify the effect of E23K and I337V in the KCNJ11 gene on susceptibility to impaired glucose regulation, we conducted a case control study in 1125 essential hypertension patients with or without impaired glucose regulation among a Han Chinese population. We also evaluated the impact of two SNPs on insulin sensitivity and glucose tolerance estimated through an oral glucose tolerance test. In our case control study, no association of E23K and I337V with impaired glucose regulation was found using any genotypic models. However, lysine carriers of E23K showed a significant association with decreased insulin (30 min) and Cederholm index, and valine carriers of I337V showed association with a lower Cederholm index. All the quantitative tests were performed by linear regression, with adjustment for gender, age, body mass index, blood pressure, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. These findings provided evidence that the KCNJ11 gene plays a role in the pathogenesis of decreased insulin sensitivity in essential hypertension patients.

Association between Genotype and the Glycemic Response to an Oral Glucose Tolerance Test: A Systematic Review

“…A total of 49 eligible reports investigated the association between SNPs and the gAUC after an OGTT in 39 different cohorts, i.e., Quebec Family Study [ 12 , 13 , 14 , 15 , 16 , 17 ], Amish Family Diabetes Study [ 18 , 19 ], Ely Study [ 20 ], Tübingen Family Study (TÜF) [ 21 ], European Atherosclerosis Research Study (EARS II) [ 22 , 23 ], Sapphire Study [ 24 ], Metabolic Intervention Cohort Kiel (MICK) [ 25 , 26 ], European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) [ 27 , 28 ], Metabolic Syndrome in Men (METSIM) [ 28 ], Metabolic Syndrome Berlin Potsdam Study (MESYBEPO) [ 29 ], Lifestyle Intervention in a General Population for Prevention of Ischaemic Heart Disease (Inter99) [ 30 , 31 ], Berlin Ernährung Geschwister Study (BErG-Study) [ 32 ], and further 27 cohorts without a specific study name [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ...…”

“…In one study, a glucose amount of either 50 or 75 g was used without any justification [ 42 ]. While in most of the reports, the duration of the OGTT lasted 120 min [ 20 , 21 , 22 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 36 , 37 , 38 , 39 , 41 , 43 , 44 , 45 , 47 , 48 , 50 , 52 , 53 , 54 , 56 , 57 , 58 , 59 , 60 ] or 180 min [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 35 , 40 , 42 , 49 , 51 , 55 ], in either two reports the OGTT was performed over 240 min [ 25 , 26 ] or 300 min [ 34 , 46 ].…”

“…In total, the association between SNPs and gAUC after an OGTT was assessed for 13 genes and 53 different SNPs. The most frequently examined genes included transcription factor 7 like 2 ( TCF7L2 ) with 15 eligible reports ( Table 1 ) [ 12 , 13 , 18 , 20 , 21 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 58 , 60 ], followed by peroxisome proliferator-activated receptor gamma ( PPARγ ) with ten reports ( Table 2 ) [ 14 , 15 , 22 , 24 , 25 , 37 , 38 , 39 , 40 , 59 ], and potassium inwardly rectifying channel subfamily J member 11 ( KCNJ11 ) with six reports ( Table 3 ) [ 12 , 13 , 33 , 34 , 35 , 36 ]. Furthermore, the following gene loci have been investigated in three to five reports: adiponectin ( ADIPOQ ) [ 16 , 24 , 26 ], CDK5 regulatory subunit-associated protein 1-like 1 ( CDKAL1 ) [ 12 , 13 , 21 , 28 ], cyclin-dependent kinase inhibitor-2A/B ( CDKN2A/2B ) [ 12 , 13 ,…”

“…The KCNJ11 gene locus was examined for an association with gAUC after an OGTT in six cohorts ( Table 3 ) [ 12 , 13 , 33 , 34 , 35 , 36 ]. Within the KCNJ11 gene locus, five SNPs were investigated, of whom three SNPs were examined in one cohort [ 12 , 13 ].…”

Association between potassium channel SNPs and essential hypertension in Xinjiang Kazak Chinese patients

“…In the present case-control study, the association of KCNJ11 (rs5219 and rs2285676) and KCNMB1 (rs11739136) gene polymorphisms with EH was explored in a Kazak population. Previous studies have demonstrated that there is an association between different KCNJ11 SNPs and EH and diabetes in different populations ( 33 – 35 ). However, to the best of our knowledge, there are no studies that have been performed with these SNPs in the Kazak population.…”