title: Analysis of association among clinical features and shorter leukocyte telomere length in mitochondrial diabetes with m.3243A>G mitochondrial DNA mutation.
abstract: BACKGROUND
  Mitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondria. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes with m.3243 A>G mitochondrial DNA mutation and to investigate the mechanism in this kind of diabetes by analyzing the relationship among clinical phenotypes and peripheral leukocyte DNA telomere length.
  
  
  METHODS
  Fifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243 A>G mitochondrial DNA mutation. One hundred patients with type 2 diabetes and one hundred healthy control subjects were recruited to participate in the study. Sanger sequencing was used to detect the m.3243 A>G mitochondrial DNA mutation. The peak height G/A ratio in the sequence diagram was calculated. Real-time polymerase chain reaction (PCR) was used to measure telomere length.
  
  
  RESULTS
  The patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m(2)), early onset of diabetes (35.0 ± 14.6 years) and deafness. The peak height G/A ratio correlated significantly and negatively with the age at onset of diabetes (≦ 25 years, 61.6 ± 20.17%; 25-45 years, 16.59 ± 8.64%; >45 years, 6.37 ± 0.59%; p = 0.000). Telomere length was significantly shorter among patients with mitochondrial diabetes and type 2 diabetes than in the control group (1.28 ± 0.54 vs. 1.14 ± 0.43 vs. 1.63 ± 0.61; p = 0.000). However, there was no significant difference between patients with mitochondrial diabetes and those with type 2 diabetes. There was no correlation between telomere length and the peak height G/A ratio.
  
  
  CONCLUSIONS
  Deafness with definite maternal inheritance and normal BMI, associated with elevated blood lactic acid and encephalomyopathy, for the most part, suggest the diagnosis of mitochondrial diabetes . The peak height G/A ratio could reflect the spectrum of age at onset of the disease. Telomere length was shorter in patients with mitochondrial diabetes and those with type 2 diabetes, which suggests that the shorter telomere length is likely involved in the pathogenesis of diabetes but is not specific for this kind of diabetes.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
authors.forename: Mei-Cen
authors.initials: MC
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Min
authors.affiliation: Hongshan Traditional Chinese Medicine Hospital, Chifeng City, Inner Mongolia, 024076, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Ji
authors.affiliation: Metabolic Disease Hospital of Tianjin Medical University, Tianjin City, 300000, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
authors.forename: An-Li
authors.initials: AL
authors.lastname: Tong
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Xu
authors.affiliation: Nanyang City Center Hospital, Nanyang City, Henan, 473003, China.
authors.forename: Zeng-Yi
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China. liyuxiu@medmail.com.cn.
authors.forename: Yu-Xiu
authors.initials: YX
authors.lastname: Li
mesh_terms: D000225:Adenine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016615:Telomere / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D006147:Guanine; D000225:Adenine