Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population.
OBJECTIVE
The gene encoding transcription factor 7-like 2 (TCF7L2) has been related to type 2 diabetes in multiple ethnic groups. Here, we investigate whether three single nucleotide polymorphisms (SNPs) in the TCF7L2 gene are associated with an impaired proinsulin:insulin ratio.


METHODS
In this study we examined the associations between SNPs rs7901695, rs7903146 and rs12255372 in the TCF7L2 gene and metabolic variables affecting type 2 diabetes in a population-based study of 706 unrelated individuals (47% men and 53% women; aged 35-74 years) from the province of Segovia in central Spain (Castille), including 180 individuals with type 2 diabetes.


RESULTS
The minor allele frequency of rs7901695, rs7903146 and rs12255372 was significantly higher in diabetic patients compared with that in non-diabetic individuals. The T (minor) allele of the variant rs7903146 was significantly associated with a greater OR for type 2 diabetes adjusted for age, sex and BMI in logistic regression analysis: OR 1.29 (95% CI 1.06-1.57, p = 0.01). This risk allele was also associated with an increased proinsulin:insulin ratio after OGTT. Similar results were obtained for the other TCF7L2 SNPs.


CONCLUSIONS
Our results provide further evidence supporting the belief that the TCF7L2 gene is a major determinant of type 2 diabetes risk in Spain, as in other southern European populations. The association with increased proinsulin:insulin ratio after an OGTT suggests that TCF7L2 might be involved in insulin synthesis and processing.
González-Sánchez
J L
JL
Department of Internal Medicine II, Hospital Clínico San Carlos, Madrid, Spain.
Martínez-Larrad
M T
MT
Zabena
C
C
Pérez-Barba
M
M
Serrano-Ríos
M
M
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity; D005215:Fasting; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011384:Proinsulin / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors; D013030:Spain; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D007328:Insulin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D011384:Proinsulin