Sunday, February 04, 2007

Diabetes, Mitochondria, Asians, adaptation to cold

This paper (see below) makes some interesting connections between diabetes related phenotyes, the role of mitochondria, and selection for adaptation to the cold. I don't quite "get it".

an excerpt from the conclusion:

Mitochondrial haplogroup N9a has a great diversity in the whole of China and Korea. In Japan, this haplogroup was not detected in aboriginal Ainu and Ryukyuans but only in mainland Honshu Japanese. This distribution suggests that this haplogroup was derived from the new immigrant, or Yayoi, people. These so-called mammoth hunters who had adapted to extremely cold climates in Siberia migrated back to the northern part of China ∼6,000 years ago. A part of this continental population immigrated into Japan through the Korean peninsula ∼2,900 years ago, and this immigration started the Yayoi period. Haplogroup N9a was not detected in tooth DNA from the remains of an individual from the Japanese Neolithic period, known as the "Jomon" period, whereas N9a was recently detected in the Yayoi remains at the Kuma-Nishioda site in the northern part of Kyushu Island (K. Shinoda [National Science Museum, Tokyo], personal communication). Thus, haplogroup N9a might be one of the mitochondrial haplogroups that had been selected for adaptation to cold climates. This historical character of haplogroup N9a might be relevant to resistance against T2DM by individuals who carry this haplogroup. These hypotheses, however, must be examined further by functional analysis of this haplogroup.


According to the Wallace theory, adaptation to a cold climate might involve uncoupling of electron transfer with ATP production, to increase heat production.15,16 Thus, increased mitochondrial respiration and energy expenditure is essential to meet the ATP requirement. Such an uncoupling phenotype would be protective against the development of obesity and, consequently, T2DM. However, at present, we do not have evidence that N9a is associated with lean body status. Alternatively, the uncoupling phenotype might be related to decreased mitochondrial oxidative stress, which might in turn exert a protective effect against T2DM. Further functional analysis of cybrids carrying haplogroup N9a will be necessary to verify these hypotheses.

Mitochondrial Haplogroup N9a Confers Resistance against Type 2 Diabetes in Asians

Noriyuki Fuku, Kyong Soo Park, Yoshiji Yamada, Yutaka Nishigaki, Young Min Cho, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Kimihiko Kato, Kiyoshi Yokoi, Yoshinori Nozawa, Hong Kyu Lee, and Masashi Tanaka

Am. J. Hum. Genet., 80:407-415, 2007

Abstract: Because mitochondria play pivotal roles in both insulin secretion from the pancreatic cells and insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type 2 diabetes mellitus (T2DM). The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with T2DM and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with T2DM and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups (i.e., F, B, A, N9a, M7a, M7b, G, D4a, D4b, and D5). Multivariate logistic-regression analysis with adjustment for age and sex revealed that the mitochondrial haplogroup N9a was significantly associated with resistance against T2DM (P = .0002) with an odds ratio of 0.55 (95% confidence interval 0.40–0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplogroup might confer resistance against T2DM.

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