Key result
KCNQ1 rs2237895 minor C-allele linked to ~7% lower serum insulin 30 minutes after glucose load.
Why the study?
Polymorphisms in KCNQ1 have been reported to associate with type 2 diabetes, but their impact on glucose-stimulated insulin release was unclear.
Does the minor C-allele of rs2237895 KCNQ1 associate with reduced insulin release following an oral glucose load in middle-aged, treatment-naïve individuals?
Cross-Sectional (n=6,039)
Does the minor C-allele of rs2237895 KCNQ1 associate with reduced insulin release following an oral glucose load in middle-aged, treatment-naïve individuals?
Absolute Event Rate: 277% vs 299%
p-value: p=0.008
The minor C-allele of rs2237895 in KCNQ1 is associated with reduced insulin release following an oral glucose load, suggesting its role in type 2 diabetes risk is mediated through impaired beta cell function.
rs2237895 minor allele was associated with reduced insulin release; leaves open its causal contribution to type 2 diabetes risk.
BACKGROUND: Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897) on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC) 277+/-160 vs. (AC) 280+/-164 vs. (AA) 299+/-200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007), incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02) among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228. CONCLUSION: The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.
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Holmkvist et al. (2009) conducted a cross-sectional in Type 2 diabetes risk (n=6,039). Minor C-allele of KCNQ1 rs2237895 vs. Major A-allele (AA genotype) was evaluated on Serum insulin levels 30 min after an oral glucose load (p=0.008). The minor C-allele of KCNQ1 rs2237895 was associated with significantly reduced serum insulin levels 30 minutes after an oral glucose load compared to the AA genotype (277 vs 299 pmol/l, p=0.008).
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