The FTO gene

We watched the BBC Horizon programme on genetic causes of obesity, fronted by Dr Giles Yeo (good to see an ethnic East Asian presenter).

Dr Giles Yeo with some of the AA variant folk

There is a gene of quite large effect; here is what Wikipedia says:

"A study of 38,759 Europeans for variants of FTO identified an obesity risk allele. In particular, carriers of one copy of the allele weighed on average 1.2 kilograms (2.6 lb) more than people with no copies.

"Carriers of two copies (16% of the subjects) weighed 3 kilograms (6.6 lb) more and had a 1.67-fold higher rate of obesity than those with no copies.

"The association was observed in ages 7 and upwards. "

...

"In adult humans, it was shown that adults bearing the at risk AT and AA alleles at rs9939609 consumed between 500 and 1250 kJ more each day than those carrying the protective TT genotype (equivalent to between 125 and 280 kcal per day more intake).

"The same study showed that there was no impact of the polymorphism on energy expenditure. This finding of an effect of the rs9939609 polymorphism on food intake or satiety has been independently replicated in five subsequent studies (in order of publication)."

The protective allele is T while the risk allele is A at SNP site rs9939609.

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Here is what 23andMe says about my late mother, Beryl Seel, and myself.

My mother had the protective genotype, TT, and was never overweight; I'm not so lucky (AT) and had to fight to get my weight down to its current 70-71 kilograms (from 86kg in mid-2012).

We can infer that my late father, who definitely had an expanded waistline, was AT or AA. Based on family history and if pressed, I would guess AT .. and that I got unlucky.

I wrote about this 18 months ago: another Horizon programme.

Primark

Down to Primark in Broadmead, Bristol yesterday to buy jeans. A year after it had become necessary, I finally downsized my trousers from 36" waist to 34" waist; an end to looking like a silent comic.

For fun I tried on an 'ultra skinny' pair - could barely get them on - and in the mirror saw an older version of a very garrulous comic.

But no, I am not Russell Brand's embarrassing dad: they went back on the rails.

As we walked around Cabot Circus, I remarked to Clare that something very strange is happening: almost none of the shoppers we saw were fat ...

Obesity genes and me

The BBC science programme Horizon is currently running a three part series on the science of dieting. They have identified three categories of the obese and one - the 'constant cravers' - are defined by having 'obesity genes'.

It seems likely that I'm a 'constant craver'.

A little internet research provides a short list.

1. The FTO gene

As Wikipedia explains: "In 2009 variants in the FTO gene were further confirmed to associate with obesity in two very large genome-wide association studies of body mass index (BMI). It was shown that adults bearing the at-risk AT and AA alleles at rs9939609 consumed between 125 and 280 Calories per day than those carrying the protective TT genotype," (c. 5-12% of the daily allowance).

A quick search for rs9939609 confirms I'm AT at this location. No wonder I was thirteen and a half stone before starting the 5:2 diet (I'm now at 11 stone = 70 kg but not without continuing maintenance). As a carrier of one of the 'A' risk alleles my disposition to obesity is 30% higher than that of baseline TT people.

2. The MC4R gene

"Mutations in the MC4R gene account for 6-8% of obesity cases. A common variant of the MC4R gene, distributed in about 22% of the population, increases the risk for weight gain by causing increased appetite and decreased satiety. Calorie restriction through portion control and smart food choices is the best strategy for weight loss for people carrying this variant."

The relevant SNP is rs17782313 where C alleles are associated with higher body mass index (BMI). The three options are CC, CT, TT - where TT is baseline normal, CT is associated with a BMI increase of 0.22 units and CC with a BMI increase of 0.44 units. As is so often the case, the allele effects are, as you see, additive.

What am I?  Yep, it's bad: CC.

3  The ADIPOQ gene

The relevant allele is rs17366568. "A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09)." (From here).

At last some good news! I am GG at this location.

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Doubtlessly I'll return to this topic when more is known, especially as the results to-date are so personally depressing!

Weight Loss Ward (ITV)

ITV's Weight Loss Ward (about extremely fat people) has proved to be somewhat compulsive viewing. Take Doreen Thomas: age 56, height 4ft 11, and weight 31 stone. Doreen can barely move and has been living downstairs for ten months. Her glasses have been upstairs since March, apparently.

"She's tried losing weight in the past, but it's never really succeeded. If we don't do something now she probably will be dead," says her nurse.

Doreen Thomas orders treats (from Stoke Sentinel)

On-screen, Doreen comes across as crafty and manipulative. She lives on benefits, has a full-time paid-for carer and snacks incessantly on treats ordered online.

My puritan reaction is of course outrage: why are we paying this person to waste her life in this way? She even refuses an operation to insert a gastric balloon! What could possibly be the purpose of her parasitic life?

On reflection, how would it help if Doreen were transformed into a bland, everyday mediocrity? As a welfare monster she gives millions the pleasure of lip-curling moral superiority. In her own (thankfully) inimitable way she has entertained and instructed more people than many a C-list pop star.

Yes, "Weight Loss Ward" has entirely justified Doreen Thomas's life - short as it's likely to be.

Pining for the gym

What's the noun from 'pine'? Whatever - I'm suffering from gym-pining. My voice is roughened, my head stuffed and my body suffused with lethargy. I am probably surrounded by a penumbra of germs. No, going to the gym would be a bad mistake.

I caught part of a stupid Channel 5 list programme, something about dieting fads. Number forty-something was going to the gym and catching MRSA or similar from the sweat-drenched handles of a weight machine or exercise bike. I was furtively looking up 'cotton gym gloves' when Clare discovered me and I was roundly abused as a 'Jesse': the shame.

In 'The Fast Diet' Dr Michael Mosely links obesity to cancer. The population statistics are compelling but what's the mechanism? Apparently, fat doesn't just sit there inertly, it causes chronic inflammation. This suppresses DNA repair processes which facilitates the production of cancerous cells.

Then, in a further twist, the immune system response we call inflammation is recruited by the tumour to improve its blood supply and even to facilitate metastasis. It's so not good to be overweight (he said with the zeal of the convert).