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Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.

ABSTRACT: BACKGROUND: Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information. METHODS: To test this hypothesis we set out to investigate whether mtDNA genetic variants will be differentially associated with T2DM depending on the diabetes status of the parents. To this end, association of mtDNA genetic backgrounds (haplogroups) with T2DM was assessed in 1055 Jewish patients with and without T2DM parents ('DP' and 'HP', respectively). RESULTS: Haplogroup J1 was found to be 2.4 fold under-represented in the 'HP' patients (p = 0.0035). These results are consistent with a previous observation made in Finnish T2DM patients. Moreover, assessing the haplogroup distribution in 'DP' versus 'HP' patients having diabetic siblings revealed that haplogroup J1 was virtually absent in the 'HP' group. CONCLUSION: These results imply the involvement of inherited factors, which modulate the susceptibility of haplogroup J1 to T2DM.

SUBMITTER: Feder J

PROVIDER: S-EPMC2706816 | biostudies-other | 2009

REPOSITORIES: biostudies-other

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Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.

Feder Jeanette J Ovadia Ofer O Blech Ilana I Cohen Josef J Wainstein Julio J Harman-Boehm Ilana I Glaser Benjamin B Mishmar Dan D

BMC medical genetics 20090618

<h4>Background</h4>Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of huma ...[more]

PMID: 19534826

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Project description:ImportanceLow socioeconomic status is associated with higher all-cause mortality and risks for aging-related diseases. Biological aging is a potential process underlying health conditions related to social disadvantages, which may be present from birth onward.ObjectiveTo evaluate the association of parental socioeconomic status with telomere length (TL) at birth, a marker of biological aging.Design, setting, and participantsThis prospective birth cohort study was conducted among 1504 mother-newborn pairs in Belgium recruited between February 1, 2010, and July 1, 2017.ExposuresParental socioeconomic measures, including maternal educational level, occupation, paternal educational level, and neighborhood income based on median annual household income.Main outcomes and measuresMean relative TL was measured in cord blood and placental tissue. By constructing a principal component, an integrative socioeconomic measure was derived that integrates parental socioeconomic status and neighborhood income. Multivariable adjusted regression analyses were performed to associate the integrative socioeconomic measure and TL at birth.ResultsIn 1026 newborns (517 boys; mean [SD] gestational age, 39.2 [1.4] weeks), a higher socioeconomic status was associated with longer cord blood TL and placental TL. Each unit increment in the integrative socioeconomic status measure was associated with 2.1% (95% CI, 0.9%-3.4%; P < .001) longer cord blood TL in boys, while no association was observed for girls (0.5% longer cord blood TL; 95% CI, -0.9% to 1.8%; P = .50). The sex-specific socioeconomic status interaction revealed a stronger association in boys compared with newborn girls (1.6%; 95% CI, 0.02%-3.3%; P = .047 for interaction). In placental tissue, higher socioeconomic status was associated with 1.8% (95% CI, 0.3%-3.3%; P = .02) longer TL in newborn boys but not in girls (0.4% longer TL; 95% CI, -1.2% to 2.0%; P = .63). For placental tissue, no sex and socioeconomic status interaction on TL was observed (1.4%; 95% CI, -0.5% to 3.4%; P = .16 for interaction).Conclusions and relevanceThis study suggests that parental socioeconomic status is associated with newborn TL, especially in boys. The results indicate that familial social economic factors are associated with the potential cellular longevity of the next generation, with a potential higher transgenerational vulnerability for newborn boys.

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Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.

Publications

Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.

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