Genetic Variations in the Kir6.2 Subunit(KCNJ11)of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan

Abstract

To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading.

Prediabetes is associated with genetic variations in the gene encoding the Kir6.2 subunit of the pancreatic ATP‐sensitive potassium channel (KCNJ11): A case‐control study in a Han Chinese youth population

“…Consistent with previous studies in populations with T2D, we showed in the present study that youth with prediabetes had a higher E23K carrier rate of KCNJ11 than normal subjects, and that K allele‐containing genotypes are independent risk factors for prediabetes in Chinese youth. However, in contrast with the study of Jiang et al we did not find that fasting insulin levels are independent risk factors for prediabetes in Chinese youth. Rather, we showed that lower insulin levels at 30 min during the OGTT are independent risk factors of prediabetes in Chinese youth, suggesting that impaired insulin secretion is a predictor of the development of prediabetes in Chinese youth.…”

“…In addition, mutations of KCNJ11 can cause permanent hyperinsulinemic hypoglycemia of infancy . Although the association of the E23K polymorphism with type 1 diabetes was not statistically significant in Asian and European populations, it has been reported that E23K polymorphisms of KCNJ11 contribute to T2D in youth in Taiwan . Consistent with previous studies in populations with T2D, we showed in the present study that youth with prediabetes had a higher E23K carrier rate of KCNJ11 than normal subjects, and that K allele‐containing genotypes are independent risk factors for prediabetes in Chinese youth.…”

“…Similarly, previous studies have shown that insulin secretion is significantly reduced in both heterozygous (E/K) and homozygous (K/K) variants among adults with normal glucose tolerance . However, another study on a Chinese population with T2D showed that children with normal glucose tolerance and K allele‐carrying genotypes had a higher insulin response after oral glucose loading . Given that the present study only focused on a prediabetic youth population, this discrepancy may be due, in part, to the subjects that were involved in the studies.…”

“…In the present study, the K allele‐containing genotypes (EK and KK) were found to be independent risk factors for the development of prediabetes, with a relatively high OR of 3.25 in Han Chinese youth. A similar study on Han Chinese youth in Taiwan showed that K allele‐containing genotypes are independent risk factors for the development of T2D with a relatively high OR of 4.105 . Prediabetes and T2D are complex disorders that may have an etiology in the interactions between multiple genes or environmental factors.…”

Polymorphisms Glu23Lys of KCNJ11 gene are associated with Type 2 diabetes in the Kyrgyz Population

“…Так, носитель-ство аллеля 23Lys повышает риск развития СД2 в китайской [OR= 1,15 Таким образом, данные литературы и результа-ты наших исследований показывают, что поли-морфный локус Glu23Lys гена KCNJ11 является важным генетическим фактором риска развития СД2 как в азиатских, так и в европейских популяци-ях. Частота встречаемости аллеля риска -23Lys гена KCNJ11 в кыргызской популяции составляет 0,33 и существенно не отличается от таковой в дру-гих азиатских популяциях и среди европейцев (0,34-0,37) [12,[14][15][16][17].…”