Friday 11 January 2013

Rh Negative Related Health Genetics


Sardinian Lady
Rh Negative Blood Linked To The High Amount of Diabetes Type 1 in Sardinians.

Type 1 diabetes among Sardinian children is increasing: the Sardinian diabetes register for children aged 0-14 years (1989-1999).

Casu A, Pascutto C, Bernardinelli L, Songini M.

Source

Department of Internal Medicine, Azienda Ospedaliera Brotzu, Via Peretti, Cagliari, Italy.

Abstract

OBJECTIVE:

The Sardinian type 1 diabetes register represented the basis to determine the most recent trends and the age distribution of type 1 diabetes incidence among Sardinians <15 years of age during 1989-1999. Part of the data (1989-1998) has been already published by the EURODIAB Group with a lower completeness of ascertainment (87%). The geographical distribution of type 1 diabetes risk was also investigated.

RESEARCH DESIGN AND METHODS:

The new cases of type 1 diabetes in children aged 0-14 years in Sardinia were prospectively registered from 1989 to 1999 according to the EURODIAB ACE criteria. The completeness of ascertainment calculated applying the capture-recapture method was 91%. Standardized incidence rates and 95% CI were calculated assuming the Poisson distribution. Trend of type 1 diabetes incidence was analyzed using the Poisson regression model. Maps of the geographical distribution of type 1 diabetes risk for the whole time period and separately for 1989-1994 and 1995-1999 were produced applying a Bayesian method.

RESULTS:

A total of 1214 type 1 diabetic patients were registered yielding to an overall age- and sex-standardized incidence rate of 38.8/100000 (95% CI 36.7-41.1). There was a male excess with an overall male-to-female ratio of 1.4 (1.3-1.8). The increase of incidence during the 11 years analyzed was statistically significant (P = 0.002) with a yearly increasing rate of 2.8% (1.0-4.7). No evidence of an effect of age and sex on this trend has been found. The geographical distribution of type 1 diabetes relative risk (RR) showed that the highest risk areas are located in the southern and central-eastern part of the island and the lowest risk in the northeastern part, even if most of these differences were not statistically significant. This geographical distribution seemed to remain mainly the same between 1989-1994 and 1995-1999.

CONCLUSIONS:

The homogeneity of diabetes risk and the increase of incidence over the age-groups in the Sardinian population stress the role of an environmental factor uniformly distributed among the genetically high-risk Sardinians.[1]

Sardinian DNA
About 42% of the Sardinians belong to Y-chromosome haplogroup I. The second most common Y-chromosome haplogroup among Sardinian male population is the haplogroup R1b (22% of the total population) mainly present in the northern part of the island. Sardinia also has a relatively high distribution of Y-chromosome haplogroup G (11%), which is also found in the Caucasus, the Pyrenees and the Alps, in particular Tyrol area. Other haplogroups show lower frequencies.

Note: These health problems then seem to be related to the I haplogroup and Rh negative blood parts of the island, but not R1b areas.

The most common mtDNA haplogroups in Sardinia are H (H1 and H3) and V who are also particularly common in the iberian peninsula. Some subclades typical of Sardinia and rare in the rest of Europe are:

The subclade U5b3a1 of Haplogroup U (mtDNA), about 4% of the female population in Sardinia belongs to this haplotype. One other interesting anomaly is the presence of H13a of Haplogroup H (mtDNA) is present in the island at around 9.2%. As this is an extremely rare subclade normally present in the Caucasus, its worthy of further investigation.[2]

RH blood groups and diabetic disorders: is there an effect on glycosylated hemoglobin level?
Hum Biol. 2000 Apr;72(2):287-94.
Gloria-Bottini F, Antonacci E, Bottini N, Ogana A, Borgiani P, De Santis G, Lucarini N.
  • Recent cloning of RH genes has elucidated their structure, suggesting that RH proteins are part of an oligomeric complex with transport function in the erythrocyte. This observation prompted us to investigate a possible relationship between the RH system and the glycosylated hemoglobin level (Hb A(1c)) in diabetes. This compound is considered an important indicator- of glycemic control in diabetic disorders. We studied 278 subjects with non-insulin-dependent diabetes mellitus (NIDDM) from the population of Penne, Italy. Glycemic and glycosylated hemoglobin (Hb A(1c)) levels are associated with RH phenotype. Glucose and Hb A(1c) levels are increased in DCcEe subjects and decreased in ddccee subjects as compared to the mean values for other genotypes. Sex, age at onset of disease, duration of disease, and age of patients were also considered. Correlation analysis suggests that these variables influence glycemia directly and Hb A(1c) indirectly. The RH system, on the other hand, seems to influence the Hb A(1c) level directly. Preliminary data on 53 children with insulin-dependent diabetes mellitus (IDDM) from Sardinia seem to confirm the relationship between RH and Hb A(1c) observed in NIDDM. Since glycosylated hemoglobin is found inside red blood cells, the relationship between RH genetic variability and Hb A(1c) level suggests that RH proteins may influence glucose transport through red cell membrane and/or hemoglobin glycation.[3]

Type 1 Diabetes is linked to other genetic traits of Rh Negatives through SNP data:

SNP Rs2476601

This SNP, located in the PTPN22 gene and also known as R620W, or 1858C>T, may influence Rheumatoid Arthritis and other autoimmune diseases, including but not limited to, multiple sclerosisCrohn's diseaseceliac disease and type-1 diabetes.
In an expanded follow-up study of >6,000 controls and 6,000 patients, the heterozygote odds ratio for type-1 diabetes for this SNP was recalculated to be 1.98 (CI 1.82-2.15). [PMID 17554260]

rs2476601 was confirmed in another 2007 study to be a risk factor for RA [PMID 17804836].

rs2476601 shows a 0.75 (r squared) correlation with rs6679677, a SNP in the RSBN1 gene associated with rheumatoid arthritis. [PMID 17554300]

[PMID 17934143]] Confirms association of rs2476601 with type-1 diabetes in a Sardinian population of 490 sporadic patients (794 families).
[PMID 18301444] In study of 332 Norwegian patients plus a meta-analysis, the rs2476601(A) allele was linked to autoimmune Addison's disease (p=0.003)
[PMID 18305142rs2476601(A) has a higher relative risk in type-1 diabetes cases carrying lower risk HLA class II genotypes than in those carrying higher risk ones (p=1.36x10-4 in a test of interaction).[4]

Linking PTPN22 with HLA-B27 which is associated with many autoimmune diseases, where as the SNP is associated with various others including Diabetes.

Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis.
Conclusion

PTPN22 rs2476601 is associated with HLA-B27 which in turn is associated with Rh negative blood and all the related health problems, including but not limited to: Type 1 diabetes, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, multiple sclerosis, Crohn's disease, psoriasis, ankylosing spondylitus.

These health problems are particularly virulent in those with ftDNA I and mtDNA H.

Sources

[1] Type 1 diabetes among sardinian children is increasing - ncbi.nlm.nih.gov/pubmed/15220238
[2] DNA of Sardinians - nature.com/ejhg/journal/v11/n10/full/5201040a.html
[3] Diabetic Disorders linked to Diabetes Type 1 - generativemedicine.org/wiki/wiki.pl/Rhesus_(Rh)_Blood_Group
[4] SNP Rs2476601 - snpedia.com/index.php/Rs2476601
[5] Linking PTPN22 with HLA-B27 - http://europepmc.org/articles/PMC3224698/?report=abstract

Research by Tia L Douglass of NATA

2 comments:

  1. I am 0- and I stop watches and seem to interfere with electricals - my computor plays up quite often for no apparent reason. I have blue eyes and fair hair, and am intuitive (saw a ghost at three and scared my poor Aunt - it was her Tudor era home in Somerset. Have had other experiences since - not all of them pleasant)

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  2. Take 1 teaspoon of local organic honey, dusted with cinnamon. Twice a day, it's curse up to 500 different deseases and conditions including type 1 and type 2 Diabetes. 🌈🐍🌈

    ReplyDelete