Strong Parent-of-Origin Effects in the Association of KCNQ1 Variants With Type 2 Diabetes in American Indians

Autor: Robert L. Hanson, Tingwei Guo, Sayuko Kobes, Leslie J. Baier, Jamie Fleming, William C. Knowler, Clifton Bogardus, Yunhua L. Muller
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Adult
Male
Parents
medicine.medical_specialty
Genotype
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Population
Kruppel-Like Transcription Factors
030209 endocrinology & metabolism
Nerve Tissue Proteins
Type 2 diabetes
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
0302 clinical medicine
Polymorphism (computer science)
Internal medicine
Diabetes mellitus
Insulin Secretion
Internal Medicine
medicine
Humans
Insulin
Genetic Predisposition to Disease
Longitudinal Studies
Allele
education
Alleles
Genetic Association Studies
030304 developmental biology
Original Research
Sp Transcription Factors
0303 health sciences
Glucose tolerance test
education.field_of_study
medicine.diagnostic_test
Genetics/Genomes/Proteomics/Metabolomics
Odds ratio
Glucose Tolerance Test
medicine.disease
Endocrinology
Diabetes Mellitus
Type 2
Haplotypes
KCNQ1 Potassium Channel
Indians
North American
Female
Zdroj: Diabetes
ISSN: 1939-327X
0012-1797
Popis: Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499), and KCNQ1 (rs2237892, rs231362). We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7,351 Pima Indians from 4,549 nuclear families; 34% of participants had diabetes. In a subset of 287 normoglycemic individuals, acute insulin secretion was measured by an intravenous glucose tolerance test. Statistically significant (P < 0.05) parent-of-origin effects were seen for association with type 2 diabetes for all variants. The strongest effect was seen at rs2299620 in KCNQ1; the C allele was associated with increased diabetes when maternally derived (odds ratio [OR], 1.92; P = 4.1 × 10−12), but not when paternally derived (OR, 0.93; P = 0.47; P = 9.9 × 10−6 for difference in maternal and paternal effects). A maternally derived C allele also was associated with a 28% decrease in insulin secretion (P = 0.002). This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2, and KCNQ1. In Pima Indians, the effect of maternally derived KCNQ1 variants appears to be mediated through decreased insulin secretion and is particularly strong, accounting for 4% of the variance in liability to diabetes.
Databáze: OpenAIRE
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