title: Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns.
abstract: Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P=0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P=0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.
authors.affiliation: Department of Genetics, University of North Carolina, 4109-F Neurosciences Research Building, 103 Mason Farm Road, CB#7264, 27599-7264, Chapel Hill, NC, USA. mohlke@med.unc.edu
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Scott
authors.forename: Erin C
authors.initials: EC
authors.lastname: Peck
authors.forename: Yong D
authors.initials: YD
authors.lastname: Suh
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chines
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Narisu
authors.initials: N
authors.lastname: Narisu
authors.forename: Sareena
authors.initials: S
authors.lastname: Enloe
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D004272:DNA, Mitochondrial; D007328:Insulin; D000255:Adenosine Triphosphate; D005947:Glucose