It has been known for decades that having the gum disease periodontitis increases a person’s risk for heart attack (free registration required), stroke and other forms of cardiovascular disease. Research suggests that the link is due to inflammation in the gums causing an immune reaction throughout the entire body. That can increase blood pressure and encourage the accumulation of atherosclerotic plaques in the arteries.

Now researchers have drawn a genetic link between periodontitis and heart disease as well. It turns out that variations in a region of chromosome 9 that have already been associated with heart disease also influence a person’s chances of developing periodontitis.

The specific genetic marker identified by the study is not part of the 23andMe Personal Genome Service. But another marker that has also been linked to heart disease and lies in the same chromosomal neighborhood is described in the Heart Attack research report.

Arne Schäfer of the Institute for Clinical Molecular Biology in Kiel, Germany presented the research in Vienna, Austria, last week at the annual meeting of the European Society of Human Genetics. He and his colleagues found that people with a marker for increased cardiovascular risk in a stretch of DNA known as 9p21 were more likely to have gum disease as well.

The high-risk version of the marker increased a person’s chances of having generalized aggressive periodontitis by 1.99 times, and localized aggressive periodontitis 1.72 times. Aggressive periodontitis generally strikes early in life and progresses rapidly, leading to tooth loss as early as age 20.

The 9p21 region of chromosome 9 contains several genes involved in suppressing the proliferation of cells. In a recent PLoS Genetics paper the researchers suggest that the variation they studied somehow affects the function of one of these genes.

Rather than superceding previous findings linking the effects of periodontal inflammation itself on heart disease, the researchers said, their study provides valuable additional information that could help unravel the connection between the two conditions.

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No matter when it happens, puberty is no fun.  But for girls, entering womanhood earlier or later than average can mean more than just the social awkwardness of being quick to mature or a late bloomer.  It can have important health consequences later in life.

In general, girls in the developed world are maturing faster now than ever before.  In the mid-nineteenth century the age at menarche (the first menstrual period, a milestone usually reached about two to three years after puberty begins) was about 16, but by the end of the twentieth century that number had fallen to about 13. Earlier age at menarche has been associated with an increased risk for breast, ovarian and endometrial cancer. On the other hand, later menarche is linked to increased risk for osteoporosis and cardiovascular disease.

Much of the change in the rate of maturation for girls has been attributed to better nutrition and rising rates of obesity, but new research shows that the age at menarche is also influenced by genetics.

Four papers (Ong et al., Sulem et al., Perry et al., and He et al.), published online yesterday in the journal Nature Genetics, analyzed data from a total of more than 60,000 women with European ancestry and identified two regions of the genome that contain variations associated with small differences in age at menarche.  One of these four studies, and a fifth paper (Stolk et al.), also found variations associated with the timing of menopause, the other end of the reproductive spectrum for women.

All four studies looking at age of menarche found a connection with a region of chromosome 6. Each paper identified slightly different variants, but they all appear to be zeroing in on a single, yet to be found, causative variation in the DNA.  As an example of the effect of the chromosome 6 SNPs, Ong et al. found that compared to those with two Cs, each T at rs314263 meant that woman got her first period about six weeks earlier.

(Ong et al. actually looked at rs314276, but we’re focusing on rs314263, a perfect proxy for the original SNP.  23andMe customers can check their data for rs314263 using the Browse Raw Data feature.)

Each T at rs314263 was also associated with 1.20 times greater odds of breast development at age 10, 1.26 times greater odds of advanced breast development between the ages of 9 and 16 and a faster rate of increase in height and weight.

Although girls who go through puberty earlier than their peers are tall for their age during childhood, their growth stops sooner and they are generally shorter as adults.  Ong et al. found that each T at rs314263 was associated with a reduction in adult height of about 0.15 inches.

Two studies also found an association between variations on chromosome 9 with age at menarche.  Each C at rs7861820 (the most significant SNP found in He et al.), for example, translated into about five weeks earlier menarche.

He et al. and Stolk et al. found variations in five regions of the genome associated with another big change in a woman’s life: menopause. The risks associated with the timing of menopause are the reverse of those associated with menarche: later menopause has been associated with higher risk for certain cancers and earlier menopause is linked to increased risk for osteoporosis and cardiovascular disease.

(23andMe customers can check their data for SNPs representative of these five regions using the table at the end of this post.)

Finally, all of you boys and men out there need not feel left out:  Ong et al. also looked at the effects of rs314263 on puberty in males.  They found that each copy of an T translated into 1.26 greater odds of advanced voice breaking at age 15, 1.19 times greater odds of advanced pubic hair at age 13, faster rate of growth at age 10 and about a tenth of an inch less in adult height.

SNPs Associated With Menopause

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For the millions of Americans who suffer from migraines, the risk of throbbing pain that can last for days is plenty to worry about.  But studies have shown that having a propensity for these severe and sometimes disabling headaches can also increase the risk for cardiovascular events such as stroke and heart attack.

In new report published this week in Neurology, researchers using data from the Women’s Health Study suggest that only those women with a specific genetic variation and whose migraines include aura, a type of visual disturbance characterized by flashing lights and patterns, are at increased risk for cardiovascular disease (CVD).

Previous studies have attempted to link both migraines and CVD with a variation referred to as the D/I polymorphism in ACE, a gene that encodes a blood vessel-constricting protein.  Drugs that inhibit the ACE protein are used to treat migraines and CVD.

In a study that included 25,000 women with European ancestry, about 3,200 of whom had migraines, Schürks et al. found no association of the D/I polymorphism with the headaches. Over 12 years of follow-up, there were 625 cardiovascular events (mainly strokes and heart attacks) in the group, but again, no association with the D/I polymorphism.

When the researchers took genetics out of the equation, they found that a woman with a history of any type of migraine was about 30% more likely to have CVD.  But when they added genetics back in and also divided the migraneurs (people who get migraines) up based on the presence or absence of aura, they found that only those women who had migraine with aura and also had the DD or DI genotype at the ACE polymorphism were at about two-fold increased risk for CVD.

(23andMe customers can check their data using SNP rs1799752 in the Browse Raw Data feature.  Data for this SNP is available only to those customers who received their data after 9/1/08, or upgraded their accounts since that date.)

Although these results may eventually help scientists understand the exactly how migraine and CVD are related to ACE, a lot of work remains to be done.  The authors themselves warn that larger studies will be needed and that their research did not take into account environmental or other genetic risk factors.  They also note that their study sample was restricted to Caucasian women 45 years old and older, which may mean that their results are not applicable to the population as a whole.  Finally, in both women with and without migraine, the proportion of the different genotypes (DD/DI/II) differed from what would be expected in the population, suggesting that there may have been flaws in the study.

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