Contribution of @entity5345 and @entity2674 mutations to XXXX in Pakistan.

@entity43 @entity0 @entity5344 @entity5345 @entity70944 @entity2674 @entity70945 @entity36858 @entity5 @entity70946 @entity70943 @entity70942
The population of Pakistan has been reported to have the highest rate of @entity0 of any Asian population (excluding Jews in Israel) and one of the highest rates of @entity43 worldwide. To explore the contribution that genetic factors make to these high rates, we have conducted a case-control study of 341 case subjects with @entity0 , 120 case subjects with @entity43 , and 200 female control subjects from two major cities of Pakistan (Karachi and Lahore). The prevalence of @entity5345 or @entity2674 mutations among case subjects with @entity0 was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects with @entity43 was 15.8% (95% CI 9.2%-22.4%). Mutations of the @entity5345 gene accounted for 84% of the mutations among case subjects with @entity43 and 65% of mutations among case subjects with @entity0 . The majority of detected mutations are unique to Pakistan. Five @entity5345 mutations ( @entity70942 , @entity70943 , @entity36858 , @entity70944 , and @entity70945 ) and one @entity2674 mutation ( @entity70946 ) were found in multiple case subjects and represent candidate founder mutations. The penetrance of deleterious mutations in @entity5345 and @entity2674 is comparable to that of Western populations. The cumulative risk of @entity5 to age 85 years in female first-degree relatives of @entity5345 -mutation-positive case subjects was 48% and was 37% for first-degree relatives of the @entity2674 -mutation-positive case subjects. A higher proportion of case subjects with @entity0 than of control subjects were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3; P=.001). The effects of consanguinity were significant for case subjects with early-onset @entity0 (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and case subjects with @entity43 (OR=2.4; 95% CI 1.4-4.2; P=.002). These results suggest that recessively inherited genes may contribute to @entity5344 risk in Pakistan.
