New research may help explain why multiple sclerosis rates have risen sharply in the U.S. and some other countries among women, while rates appear stable in men.The study could also broaden understanding of how environmental influences alter genes to cause a wide range of diseases. The causes of multiple sclerosis (MS) are not well understood, but experts have long suspected that environmental factors trigger the disease in people who are genetically susceptible. In the newly published study, researchers found that women with MS were more likely than men with MS to have a specific genetic mutation that has been linked to the disease.
Women were also more likely to pass the mutation to their daughters than their sons and more likely to share the MS-susceptibility gene with more distant female family members. If genes alone were involved, mothers would pass the MS-related gene to their sons as often as their daughters, said researcher George C. Ebers, MD, of the University of Oxford. Ebers’ research suggests that the ability of environmental factors to alter gene expression — a relatively new field of genetic study known as epigenetics — plays a key role in multiple sclerosis and that this role is gender-specific.
The theory is that environmental influences such as diet, smoking, stress, and even exposure to sunlight can change gene expression and this altered gene expression is passed on for a generation or two. “The idea that the environment would change genes was once thought to be ridiculous,” Ebers says. “Now it is looking like this is a much bigger influence on disease than we ever imagined.”
The study by Ebers and colleagues included 1,055 families with more than one person with MS. Close to 7,100 genes were tested, including around 2,100 from patients with the disease. The researchers were looking for MS-specific alterations in the major histocompatibility complex (MHC) gene region. They found that women with MS were 1.4 times more likely than men with the disease to carry the gene variant linked to disease risk. A total of 919 women and 302 men had the variant in the MHC region, compared to 626 women and 280 men who did not have it.
The study appeared in the Jan. 18 issue of Neurology.
Epigenetics is not evolution. Genetic alterations linked to environmental assaults can be passed down for a generation or two, but DNA usually rights itself over time, Ebers says. “This may explain why we hardly ever see MS in families over more than three generations,” he says. Earlier studies by Ebers and colleagues suggest that vitamin D deficiency may be the environmental stressor that triggers the MS-linked gene alterations. Rates of the disease are highest among people living farthest from the equator, and there is widespread speculation that lack of vitamin D due to low sun exposure may explain this. Other than Ebers’ research team, Orhun Kantarci, MD, of the Mayo Clinic in Rochester, Minn., is one of the few researches studying epigenetics as it relates to multiple sclerosis.
Kantarci calls the new research a potentially important piece of the puzzle to explain the gender difference in MS, but he adds that the research must be replicated. “This study provides more questions than answers, but it is very interesting,” he says. “We are learning that inheritance isn’t as simple as [Gregor] Mendel described.”
A popular pastime for many older people is to try and figure out their chances of getting one ailment or another. Mayo Clinic researchers have simplified it – they have figured out the lifetime risk of developing rheumatoid arthritis and six other autoimmune rheumatic diseases for both men and women. “We estimated the lifetime risk for rheumatic disease for both sexes, something that had not been done before — separately or collectively,” says Cynthia Crowson Mayo Clinic biostatistician and first author. “Prevalence and incidence rates existed, but prevalence figures underestimate individual risk and incidence rates express only a yearly estimate.”
The researchers were looking for an accurate basis to offer an easy-to-understand average risk over a person’s lifetime, knowing that risk changes at almost every age. They used data from the Rochester Epidemiology Project, a long-term epidemiology resource based on patients in Olmsted County, Minn. The cohort of 1179, consisted of patients diagnosed between 1955 and 2007, allowed the team to extrapolate the nationwide estimates.
The adult lifetime risk in the United States of having some kind of inflammatory autoimmune disease is 8.4 percent for women and 5.1 percent for men. Based on year 2000 population figures, that means one woman in 12 and one man in 20 will develop one of the conditions in their lifetime. The authors consider that a substantial risk and say their findings should encourage more research on the value of early diagnosis and intervention for people with increased genetic risk of arthritis. They hope the new figures will help in counseling patients and in fundraising efforts to find improved treatments.
The research was supported by the National Institutes of Health.
The team set out to examine levels of depression and anxiety between adults with celiac disease following a gluten-free diet and in control subjects drawn from the general population.
For their study, the team used the Hospital Anxiety and Depression Scale to measure levels of anxiety, depression, and likely anxiety or depressive disorder, in 441 adult patients with celiac disease recruited by the German Celiac Society. They then conducted the same assessments on 235 comparable patients with inflammatory bowel disease (IBD), either in remission or with slight disease activity. They did the same for the cross-sample control group of 441 adults from the general population.
The team used regression analysis to test possible demographic and disease-related predictors of anxiety and depression in celiac disease. Demographic predictors included age, sex, social class, and family status. Disease-related predictors included Latency to diagnosis, duration of GFD, compliance with GFD, thyroid disease.
The team found that female gender (P = 0.01) was the main predictor (R(2) = 0.07) of anxiety levels in patients with celiac disease. Female patients had a higher risk for a probable anxiety disorder (OR = 3.6, 95% CI: 1.3-9.4, P = 0.01) Patients who lived alone (OR = 0.5, 95% CI: 0.2-0.9, P = 0.05) enjoyed a lower risk of anxiety disorder. None of the demographic and medical variables for which the team screened predicted either depression levels or risk for a probable depressive disorders.
Patients with celiac disease showed anxiety levels of 6.6 +/- 3.4, and those with IBD, anxiety levels of 6.9 +/- 3.7, both higher than the general population's level of 4.6 +/- 3.3 – (both P < 0.001). Depression levels were similar for people with celiac disease (4.2 +/- 3.4), IBD (4.6 +/- 3.4) and the general population (4.2 +/- 3.8) (P = 0.3). Rates of likely anxiety disorders in people with celiac disease were 16.8%, and 14.0% for IBD, both higher than the rates of 5.7% in the general population (P < 0.001). All three groups showed similar rates of probable depressive disorder (P = 0.1).
Their results provide strong indications that adult women with celiac disease on a gluten-free diet suffer higher rates of anxiety than persons of the general population. They encourage clinicians to provide anxiety screens for adult women with celiac disease on a gluten-free diet.
Of the participants, 15.5%, 29.7%, 28.1%, and 21.1% reported being physically inactive at teenage, at 30 years, at 50 years, and in late life respectively; the increase in cognitive impairment for those who were inactive was between 50% and 100% at each time point. When physical activity measures for all four ages were entered into a single model and adjusted for variables such as age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and BMI, only teenage physical activity status remained significantly associated with cognitive performance in old age.
Middleton added, “As a result, to minimize the risk of dementia, physical activity should be encouraged from early life. Not to be without hope, people who were inactive at teenage can reduce their risk of cognitive impairment by becoming active in later life.”
The researchers concluded that the mechanisms by which physical activity across the life course is related to late life cognition are likely to be multi-factorial. There is evidence to suggest that physical activity has a positive effect on brain plasticity and cognition and in addition, physical activity reduces the rates and severity of vascular risk factors, such as hypertension, obesity, and type II diabetes, which are each associated with increased risk of cognitive impairment.
“Low physical activity levels in today's youth may mean increased dementia rates in the future. Dementia prevention programs and other health promotion programs encouraging physical activity should target people starting at very young ages, not just in mid- and late life,” said Middleton.
Patients who use vitamin supplements also showed lower levels of plasma homocysteine than in patients who did not (P = 0.001) or healthy controls (P = 0.003). Vitamin B6 and folate were both associated with homocysteine levels, whereas vitamin B12 was not. Twenty-four (48%) of 50 controls and 23 (50%) of 46 of the celiac disease patients carried the MTHFR thermolabile variant T-allele (P = 0.89).
The research team concludes that Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements reduces of homocysteine levels in patients with celiac disease.The study confirms earlier studies suggesting that both the presence and severity of celiac disease determined homocysteine levels.
The regular use of supplemental B vitamins resulted in higher levels of serum vitamin B6, folate, vitamin B12 and lower levels of plasma homocysteine in patients with celiac disease. Moreover, supplemental B vitamins seem to offer protection against the effects of villous atrophy on homocysteine levels, independent of the genetic susceptibility status as determined by carriage of the C677T polymorphism of 5,10 methylenetetrahydrofolate reductase.
World J Gastroenterol. 2009;15:955–960
Guinness World Records has reported the death of the world's oldest person aged 114 years and 357 days, a week shy of her 115th birthday.
Kama Chinen, a resident of a sub-tropical island in Okinawa, Japan, died on May 2, 2010. She lived to see three different centuries, the Gerontology Research Group (GRG) commented.
“Though confined to a wheelchair in her later years, Chinen enjoyed the wonders of nature and being outside,” the organization said.
Okinawa has a reputation for its long-lived residents, put down to the local diet of green tea, miso soup, vegetables, rice and fresh fish.
The title of oldest human now passes to 114-year-old Frenchwoman Eugenie Blanchard, who was born in February 1896. She lives on the Caribbean island of Guadeloupe, GRG said.
Chiyono Hasegawa, 113, in southern Japan's Saga prefecture is now the country's oldest person.
Japan has the world's highest life expectancy, and Okinawa has been home to many centenarians, a fact variously attributed to the healthy diet and environment of the island.
According to the study, old Okinawans also have lower rates of cancer, in part due to a generally low caloric, low-fat and high-fiber diet that is rich in vegetables and fruits, as well as to their physical activity.
Average life expectancy in Japan climbed sharply after World War II. In 2008, life expectancy at birth was 86.05 years for women and 79.29 years for men, according to official statistics.