GLP1R Rs3765467 Polymorphism Is Associated With The Risk Of Early-Onset Type 2 Diabetes

Abstract Objective: To investigate the relationship between glucagon-like peptide-1 receptor (GLP1R) gene polymorphisms and susceptibility to early-onset type 2 diabetes (EOD).Methods: Samples from 316 type 2 diabetes (T2DM) patients with EOD (n = 137) and late-onset T2DM (n = 179) and 145 non-diabetic individuals were analyzed. Multiplex PCR combined with resequencing HI-Reseq technology was used to detect single nucleotide polymorphisms (SNPs) of the GLP1R gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group.Results: Sixteen SNPs were identified in the exonic region of the GLP1R gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the GLP1R rs3765467 (G→A) mutation was statistically associated with EOD. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of EOD after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA+GA genotype were significantly decreased in the EOD group, and carriers of genotype AA+GA at rs3765467 had a decreased risk of EOD after adjusting for sex and body mass index. Moreover, fasting c peptide levels were significantly higher in GA+AA genotype carriers than that in GG genotype carriers.Conclusion: The GLP1R rs3765467 polymorphism was significantly associated with the age at T2DM diagnosis, and thus may be used as a marker to screen and detect individuals at risk of developing EOD.The name of the clinical trials registry: Exploration of early warning indicators for diabetic chronic complications. The approval number is 2016-004.The approval date is June 12, 2016.

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Faculty Opinions recommendation of Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726040074.793514750 ◽

2016 ◽

Author(s):

Carlos Aguilar-Salinas

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Diseases ◽

Early Onset ◽

Late Onset ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Onset Type

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Bariatric Surgery for Patients With Early-Onset vs Late-Onset Type 2 Diabetes

JAMA Surgery ◽

10.1001/jamasurg.2016.1130 ◽

2016 ◽

Vol 151 (9) ◽

pp. 798 ◽

Cited By ~ 13

Author(s):

Lwin Aung ◽

Wei-Jei Lee ◽

Shu Chun Chen ◽

Kong-Han Ser ◽

Chun-Chi Wu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Early Onset ◽

Late Onset ◽

Onset Type

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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

International Journal of Endocrinology ◽

10.1155/2014/983016 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Yi-Der Jiang ◽

Lee-Ming Chuang ◽

Dee Pei ◽

Yann-Jinn Lee ◽

Jun-Nan Wei ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Body Mass ◽

Early Onset ◽

Plasma Insulin ◽

Insulin Response ◽

Glucose Loading ◽

Fasting Plasma Insulin ◽

E23k Polymorphism

To investigate the role of E23K polymorphism of theKCNJ11gene 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 theKCNJ11gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism ofKCNJ11gene 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 theKCNJ11gene 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.

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Faculty Opinions recommendation of Bariatric Surgery for Patients With Early-Onset vs Late-Onset Type 2 Diabetes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726392900.793545962 ◽

2018 ◽

Author(s):

Naji Abumrad

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Early Onset ◽

Late Onset ◽

Onset Type

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Abstract 4880: The Common Variant Rs9939609 In The FTO Gene Is Associated With Early-onset Myocardial Infarction

Circulation ◽

10.1161/circ.118.suppl_18.s_955-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Piera A Merlini ◽

Carlo Berzuini ◽

Pier M Mannucci ◽

Flora Peyvandi ◽

Marco Tubaro ◽

...

Keyword(s):

Myocardial Infarction ◽

Type 2 Diabetes ◽

Body Mass Index ◽

Body Mass ◽

Early Onset ◽

Odds Ratio ◽

Fto Gene ◽

The Common ◽

Rs9939609 Variant

Background and objective Type 2 diabetes and increase in body mass index (BMI) are major risk factors for myocardial infarction. Recently the common variant rs9939609 in the fat mass and obesity-associated (FTO) gene was reported to associate with type 2 diabetes only through an effect on body mass index (BMI). In the present study we investigated whether rs9939609 variant in the FTO gene is directly associated with early-onset myocardial infarction. Method The Italian genetic study of early-onset myocardial infarction is a nationwide prospective case-control study involving 1842 patients hospitalised for a first myocardial infarction before the age of 45 years, and 1842 healthy subjects matched for age, gender and geographical origin. The following baseline data were collected for each case and control: age, gender, family history, body mass index, smoking habits, hypertension, hypercholesterolemia, diabetes, cocaine use, physical activity and alcohol consumption. Genotyping was performed using a Sequenome MassARRAY platform. Results The rs9939609 variant in FTO gene was significantly associated with early-onset myocardial infarction (odds ratio 1,25, 95% confidence interval 1.08 to 1.45; p=0.000015) with a multiplicative model of the effect. After adjusting for diabetes, BMI, hypercholesterolemia and smoking the rs9939609 risk allele was still significantly associated with early-onset myocardial infarction (odds ratio 1.20, 95% confidence interval 1.05–1.38; p=0.006), thus indicating that this variant has a direct effect on myocardial infarction, not mediated by BMI. As previously reported FTO genotype was also associated with an increase in BMI, more specifically the p-value of no association in the control group is equal to 0,01. Conclusions The rs9939609 variant in the FTO gene was significantly associated with the risk of early-onset myocardial infarction and with the increase in BMI. The rs9939609 variant in the FTO gene directly influences the risk of early-onset myocardial infarction.

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